Anthony Kossiakoff

Research Summary
The Kossiakoff Group's research interests are to provide a molecular understanding of how molecular recognition governs virtually all aspects of biological function. To study these issues our group employs a combination of X-ray crystallography and cryo-EM, site-directed mutagenesis, phage display and biophysical analysis. The Kossiakoff group has also pioneered a new technology called “chaperone-assisted” crystallography, which has facilitated the structural analyses of protein systems that had been totally recalcitrant to other approaches. The group has also been at the forefront of developing synthetic antibodies. These synthetic antibodies are much more powerful that traditional monoclonal antibodies and have the potential to completely replace them for uses in live cell imaging and proteomics.
Protein Engineering, Structural Biology, Phage Display Mutagenesis, Antibody Engineering, T-cell Engineering, Membrane Proteins
  • Davis and Elkins College, BS Chemistry/Math 09/1968
  • University of Delaware, Ph.D Physical Chemistry 09/1972
  • California Institute of Technology, Postdoc Structural Biology 05/1975
Biosciences Graduate Program Association
Awards & Honors
  • 1983 - 1998 Director Department of Protein Engineering Genentech, Inc.
  • 1998 - 2003 Director Institute for Biophysical Dynamics University of Chicago
  • 1998 - 2011 Chair Department of Biochemistry and Molecular Biology University of Chicago
  • 2003 - Alumni Hall of Fame University of Delaware
  • 2011 - Honorary Degree Doctor of Science Davis and Elkins College
  • 2012 - Fellow of American Association for Advancement of Science AAAS
  • 2019 - Christian Anfinsen Award Protein Society
  1. Yen YC, Schafer CT, Gustavsson M, Eberle SA, Dominik PK, Deneka D, Zhang P, Schall TJ, Kossiakoff AA, Tesmer JJG, Handel TM. Structures of atypical chemokine receptor 3 reveal the basis for its promiscuity and signaling bias. Sci Adv. 2022 07 15; 8(28):eabn8063. View in: PubMed

  2. Feng P, Wu X, Erramilli SK, Paulo JA, Knejski P, Gygi SP, Kossiakoff AA, Rapoport TA. A peroxisomal ubiquitin ligase complex forms a retrotranslocation channel. Nature. 2022 07; 607(7918):374-380. View in: PubMed

  3. Liu H, Irobalieva RN, Bang-Sørensen R, Nosol K, Mukherjee S, Agrawal P, Stieger B, Kossiakoff AA, Locher KP. Structure of human NTCP reveals the basis of recognition and sodium-driven transport of bile salts into the liver. Cell Res. 2022 08; 32(8):773-776. View in: PubMed

  4. Bley CJ, Nie S, Mobbs GW, Petrovic S, Gres AT, Liu X, Mukherjee S, Harvey S, Huber FM, Lin DH, Brown B, Tang AW, Rundlet EJ, Correia AR, Chen S, Regmi SG, Stevens TA, Jette CA, Dasso M, Patke A, Palazzo AF, Kossiakoff AA, Hoelz A. Architecture of the cytoplasmic face of the nuclear pore. Science. 2022 06 10; 376(6598):eabm9129. View in: PubMed

  5. Arrigoni C, Lolicato M, Shaya D, Rohaim A, Findeisen F, Fong LK, Colleran CM, Dominik P, Kim SS, Schuermann JP, DeGrado WF, Grabe M, Kossiakoff AA, Minor DL. Quaternary structure independent folding of voltage-gated ion channel pore domain subunits. Nat Struct Mol Biol. 2022 06; 29(6):537-548. View in: PubMed

  6. Ura M, Mukherjee S, Marcon E, Koestler SA, Kossiakoff AA. Synthetic Antibodies Detect Distinct Cellular States of Chromosome Passenger Complex Proteins. J Mol Biol. 2022 06 30; 434(12):167602. View in: PubMed

  7. Ashraf KU, Nygaard R, Vickery ON, Erramilli SK, Herrera CM, McConville TH, Petrou VI, Giacometti SI, Dufrisne MB, Nosol K, Zinkle AP, Graham CLB, Loukeris M, Kloss B, Skorupinska-Tudek K, Swiezewska E, Roper DI, Clarke OB, Uhlemann AC, Kossiakoff AA, Trent MS, Stansfeld PJ, Mancia F. Structural basis of lipopolysaccharide maturation by the O-antigen ligase. Nature. 2022 04; 604(7905):371-376. View in: PubMed

  8. Rohaim A, Slezak T, Koh YH, Blachowicz L, Kossiakoff AA, Roux B. Engineering of a synthetic antibody fragment for structural and functional studies of K+ channels. J Gen Physiol. 2022 04 04; 154(4). View in: PubMed

  9. Lim SA, Zhou J, Martinko AJ, Wang YH, Filippova EV, Steri V, Wang D, Remesh SG, Liu J, Hann B, Kossiakoff AA, Evans MJ, Leung KK, Wells JA. Targeting a proteolytic neoepitope on CUB domain containing protein 1 (CDCP1) for RAS-driven cancers. J Clin Invest. 2022 02 15; 132(4). View in: PubMed

  10. Bloch JS, Mukherjee S, Kowal J, Filippova EV, Niederer M, Pardon E, Steyaert J, Kossiakoff AA, Locher KP. Development of a universal nanobody-binding Fab module for fiducial-assisted cryo-EM studies of membrane proteins. Proc Natl Acad Sci U S A. 2021 11 23; 118(47). View in: PubMed

  11. Yan Y, Mukherjee S, Harikumar KG, Strutzenberg TS, Zhou XE, Suino-Powell K, Xu TH, Sheldon RD, Lamp J, Brunzelle JS, Radziwon K, Ellis A, Novick SJ, Vega IE, Jones RG, Miller LJ, Xu HE, Griffin PR, Kossiakoff AA, Melcher K. Structure of an AMPK complex in an inactive, ATP-bound state. Science. 2021 07 23; 373(6553):413-419. View in: PubMed

  12. Nosol K, Bang-Sørensen R, Irobalieva RN, Erramilli SK, Stieger B, Kossiakoff AA, Locher KP. Structures of ABCB4 provide insight into phosphatidylcholine translocation. Proc Natl Acad Sci U S A. 2021 08 17; 118(33). View in: PubMed

  13. Chen Q, Plasencia M, Li Z, Mukherjee S, Patra D, Chen CL, Klose T, Yao XQ, Kossiakoff AA, Chang L, Andrews PC, Tesmer JJG. Structures of rhodopsin in complex with G-protein-coupled receptor kinase 1. Nature. 2021 07; 595(7868):600-605. View in: PubMed

  14. Yu Y, Zheng Q, Erramilli SK, Pan M, Park S, Xie Y, Li J, Fei J, Kossiakoff AA, Liu L, Zhao M. K29-linked ubiquitin signaling regulates proteotoxic stress response and cell cycle. Nat Chem Biol. 2021 08; 17(8):896-905. View in: PubMed

  15. Enderle L, Shalaby KH, Gorelik M, Weiss A, Blazer LL, Paduch M, Cardarelli L, Kossiakoff A, Adams JJ, Sidhu SS. A T cell redirection platform for co-targeting dual antigens on solid tumors. MAbs. 2021 Jan-Dec; 13(1):1933690. View in: PubMed

  16. Cater RJ, Chua GL, Erramilli SK, Keener JE, Choy BC, Tokarz P, Chin CF, Quek DQY, Kloss B, Pepe JG, Parisi G, Wong BH, Clarke OB, Marty MT, Kossiakoff AA, Khelashvili G, Silver DL, Mancia F. Structural basis of omega-3 fatty acid transport across the blood-brain barrier. Nature. 2021 07; 595(7866):315-319. View in: PubMed

  17. Gallo E, Kelil A, Haughey M, Cazares-Olivera M, Yates BP, Zhang M, Wang NY, Blazer L, Carderelli L, Adams JJ, Kossiakoff AA, Wells JA, Xie W, Sidhu SS. Inhibition of Cancer Cell Adhesion, Migration and Proliferation by a Bispecific Antibody that Targets two Distinct Epitopes on av Integrins. J Mol Biol. 2021 07 23; 433(15):167090. View in: PubMed

  18. Slezak T, Kossiakoff AA. Engineered Ultra-High Affinity Synthetic Antibodies for SARS-CoV-2 Neutralization and Detection. J Mol Biol. 2021 05 14; 433(10):166956. View in: PubMed

  19. Lokareddy RK, Ko YH, Hong N, Doll SG, Paduch M, Niederweis M, Kossiakoff AA, Cingolani G. Recognition of an a-helical hairpin in P22 large terminase by a synthetic antibody fragment. Acta Crystallogr D Struct Biol. 2020 Sep 01; 76(Pt 9):876-888. View in: PubMed

  20. Tsutsumi N, Mukherjee S, Waghray D, Janda CY, Jude KM, Miao Y, Burg JS, Aduri NG, Kossiakoff AA, Gati C, Garcia KC. Structure of human Frizzled5 by fiducial-assisted cryo-EM supports a heterodimeric mechanism of canonical Wnt signaling. Elife. 2020 08 07; 9. View in: PubMed

  21. Mukherjee S, Erramilli SK, Ammirati M, Alvarez FJD, Fennell KF, Purdy MD, Skrobek BM, Radziwon K, Coukos J, Kang Y, Dutka P, Gao X, Qiu X, Yeager M, Eric Xu H, Han S, Kossiakoff AA. Synthetic antibodies against BRIL as universal fiducial marks for single-particle cryoEM structure determination of membrane proteins. Nat Commun. 2020 03 27; 11(1):1598. View in: PubMed

  22. Bloch JS, Pesciullesi G, Boilevin J, Nosol K, Irobalieva RN, Darbre T, Aebi M, Kossiakoff AA, Reymond JL, Locher KP. Structure and mechanism of the ER-based glucosyltransferase ALG6. Nature. 2020 03; 579(7799):443-447. View in: PubMed

  23. Kim J, Tan YZ, Wicht KJ, Erramilli SK, Dhingra SK, Okombo J, Vendome J, Hagenah LM, Giacometti SI, Warren AL, Nosol K, Roepe PD, Potter CS, Carragher B, Kossiakoff AA, Quick M, Fidock DA, Mancia F. Structure and drug resistance of the Plasmodium falciparum transporter PfCRT. Nature. 2019 12; 576(7786):315-320. View in: PubMed

  24. Dutka P, Mukherjee S, Gao X, Kang Y, de Waal PW, Wang L, Zhuang Y, Melcher K, Zhang C, Xu HE, Kossiakoff AA. Development of "Plug and Play" Fiducial Marks for Structural Studies of GPCR Signaling Complexes by Single-Particle Cryo-EM. Structure. 2019 12 03; 27(12):1862-1874.e7. View in: PubMed

  25. Slezak T, Bailey LJ, Jaskolowski M, Nahotko DA, Filippova EV, Davydova EK, Kossiakoff AA. An engineered ultra-high affinity Fab-Protein G pair enables a modular antibody platform with multifunctional capability. Protein Sci. 2020 01; 29(1):141-156. View in: PubMed

  26. Farcasanu M, Wang AG, Uchanski T, Bailey LJ, Yue J, Chen Z, Wu X, Kossiakoff A, Tang WJ. Rapid Discovery and Characterization of Synthetic Neutralizing Antibodies against Anthrax Edema Toxin. Biochemistry. 2019 07 09; 58(27):2996-3004. View in: PubMed

  27. Sun J, Paduch M, Kim SA, Kramer RM, Barrios AF, Lu V, Luke J, Usatyuk S, Kossiakoff AA, Tan S. Structural basis for activation of SAGA histone acetyltransferase Gcn5 by partner subunit Ada2. Proc Natl Acad Sci U S A. 2018 10 02; 115(40):10010-10015. View in: PubMed

  28. Kintzer AF, Green EM, Dominik PK, Bridges M, Armache JP, Deneka D, Kim SS, Hubbell W, Kossiakoff AA, Cheng Y, Stroud RM. Structural basis for activation of voltage sensor domains in an ion channel TPC1. Proc Natl Acad Sci U S A. 2018 09 25; 115(39):E9095-E9104. View in: PubMed

  29. Radwanska MJ, Jaskólowski M, Davydova E, Derewenda U, Miyake T, Engel DA, Kossiakoff AA, Derewenda ZS. The structure of the C-terminal domain of the nucleoprotein from the Bundibugyo strain of the Ebola virus in complex with a pan-specific synthetic Fab. Acta Crystallogr D Struct Biol. 2018 07 01; 74(Pt 7):681-689. View in: PubMed

  30. Kang Y, Kuybeda O, de Waal PW, Mukherjee S, Van Eps N, Dutka P, Zhou XE, Bartesaghi A, Erramilli S, Morizumi T, Gu X, Yin Y, Liu P, Jiang Y, Meng X, Zhao G, Melcher K, Ernst OP, Kossiakoff AA, Subramaniam S, Xu HE. Publisher Correction: Cryo-EM structure of human rhodopsin bound to an inhibitory G protein. Nature. 2018 09; 561(7724):E44. View in: PubMed

  31. Kang Y, Kuybeda O, de Waal PW, Mukherjee S, Van Eps N, Dutka P, Zhou XE, Bartesaghi A, Erramilli S, Morizumi T, Gu X, Yin Y, Liu P, Jiang Y, Meng X, Zhao G, Melcher K, Ernst OP, Kossiakoff AA, Subramaniam S, Xu HE. Cryo-EM structure of human rhodopsin bound to an inhibitory G protein. Nature. 2018 06; 558(7711):553-558. View in: PubMed

  32. Kossiakoff AA, Mukherjee S, Horn JR. Reply to Kang and Brooks: Comment on the calculations in protein thermodynamics. J Biol Chem. 2018 04 06; 293(14):5063. View in: PubMed

  33. Zhang Z, Liang WG, Bailey LJ, Tan YZ, Wei H, Wang A, Farcasanu M, Woods VA, McCord LA, Lee D, Shang W, Deprez-Poulain R, Deprez B, Liu DR, Koide A, Koide S, Kossiakoff AA, Li S, Carragher B, Potter CS, Tang WJ. Ensemble cryoEM elucidates the mechanism of insulin capture and degradation by human insulin degrading enzyme. Elife. 2018 03 29; 7. View in: PubMed

  34. Mukherjee S, Griffin DH, Horn JR, Rizk SS, Nocula-Lugowska M, Malmqvist M, Kim SS, Kossiakoff AA. Engineered synthetic antibodies as probes to quantify the energetic contributions of ligand binding to conformational changes in proteins. J Biol Chem. 2018 02 23; 293(8):2815-2828. View in: PubMed

  35. Bailey LJ, Sheehy KM, Dominik PK, Liang WG, Rui H, Clark M, Jaskolowski M, Kim Y, Deneka D, Tang WJ, Kossiakoff AA. Locking the Elbow: Improved Antibody Fab Fragments as Chaperones for Structure Determination. J Mol Biol. 2018 02 02; 430(3):337-347. View in: PubMed

  36. Rizk SS, Mukherjee S, Koide A, Koide S, Kossiakoff AA. Targeted rescue of cancer-associated IDH1 mutant activity using an engineered synthetic antibody. Sci Rep. 2017 04 03; 7(1):556. View in: PubMed

  37. Paduch M, Kossiakoff AA. Generating Conformation and Complex-Specific Synthetic Antibodies. Methods Mol Biol. 2017; 1575:93-119. View in: PubMed

  38. Sundaram KM, Zhang Y, Mitra AK, Kouadio JK, Gwin K, Kossiakoff AA, Roman BB, Lengyel E, Piccirilli JA. Prolactin Receptor-Mediated Internalization of Imaging Agents Detects Epithelial Ovarian Cancer with Enhanced Sensitivity and Specificity. Cancer Res. 2017 04 01; 77(7):1684-1696. View in: PubMed

  39. Galilee M, Britan-Rosich E, Griner SL, Uysal S, Baumgärtel V, Lamb DC, Kossiakoff AA, Kotler M, Stroud RM, Marx A, Alian A. The Preserved HTH-Docking Cleft of HIV-1 Integrase Is Functionally Critical. Structure. 2016 11 01; 24(11):1936-1946. View in: PubMed

  40. Shao Y, Huang H, Qin D, Li NS, Koide A, Staley JP, Koide S, Kossiakoff AA, Piccirilli JA. Specific Recognition of a Single-Stranded RNA Sequence by a Synthetic Antibody Fragment. J Mol Biol. 2016 10 09; 428(20):4100-4114. View in: PubMed

  41. Schaefer ZP, Bailey LJ, Kossiakoff AA. A polar ring endows improved specificity to an antibody fragment. Protein Sci. 2016 07; 25(7):1290-8. View in: PubMed

  42. Dominik PK, Borowska MT, Dalmas O, Kim SS, Perozo E, Keenan RJ, Kossiakoff AA. Conformational Chaperones for Structural Studies of Membrane Proteins Using Antibody Phage Display with Nanodiscs. Structure. 2016 Feb 02; 24(2):300-9. View in: PubMed

  43. Zhong N, Loppnau P, Seitova A, Ravichandran M, Fenner M, Jain H, Bhattacharya A, Hutchinson A, Paduch M, Lu V, Olszewski M, Kossiakoff AA, Dowdell E, Koide A, Koide S, Huang H, Nadeem V, Sidhu SS, Greenblatt JF, Marcon E, Arrowsmith CH, Edwards AM, Gräslund S. Optimizing Production of Antigens and Fabs in the Context of Generating Recombinant Antibodies to Human Proteins. PLoS One. 2015; 10(10):e0139695. View in: PubMed

  44. Stuwe T, Bley CJ, Thierbach K, Petrovic S, Schilbach S, Mayo DJ, Perriches T, Rundlet EJ, Jeon YE, Collins LN, Huber FM, Lin DH, Paduch M, Koide A, Lu V, Fischer J, Hurt E, Koide S, Kossiakoff AA, Hoelz A. Architecture of the fungal nuclear pore inner ring complex. Science. 2015 Oct 02; 350(6256):56-64. View in: PubMed

  45. Hornsby M, Paduch M, Miersch S, Sääf A, Matsuguchi T, Lee B, Wypisniak K, Doak A, King D, Usatyuk S, Perry K, Lu V, Thomas W, Luke J, Goodman J, Hoey RJ, Lai D, Griffin C, Li Z, Vizeacoumar FJ, Dong D, Campbell E, Anderson S, Zhong N, Gräslund S, Koide S, Moffat J, Sidhu S, Kossiakoff A, Wells J. A High Through-put Platform for Recombinant Antibodies to Folded Proteins. Mol Cell Proteomics. 2015 Oct; 14(10):2833-47. View in: PubMed

  46. Borowska MT, Dominik PK, Anghel SA, Kossiakoff AA, Keenan RJ. A YidC-like Protein in the Archaeal Plasma Membrane. Structure. 2015 Sep 01; 23(9):1715-1724. View in: PubMed

  47. Mukherjee S, Ura M, Hoey RJ, Kossiakoff AA. A New Versatile Immobilization Tag Based on the Ultra High Affinity and Reversibility of the Calmodulin-Calmodulin Binding Peptide Interaction. J Mol Biol. 2015 Aug 14; 427(16):2707-25. View in: PubMed

  48. Marcon E, Jain H, Bhattacharya A, Guo H, Phanse S, Pu S, Byram G, Collins BC, Dowdell E, Fenner M, Guo X, Hutchinson A, Kennedy JJ, Krastins B, Larsen B, Lin ZY, Lopez MF, Loppnau P, Miersch S, Nguyen T, Olsen JB, Paduch M, Ravichandran M, Seitova A, Vadali G, Vogelsang MS, Whiteaker JR, Zhong G, Zhong N, Zhao L, Aebersold R, Arrowsmith CH, Emili A, Frappier L, Gingras AC, Gstaiger M, Paulovich AG, Koide S, Kossiakoff AA, Sidhu SS, Wodak SJ, Gräslund S, Greenblatt JF, Edwards AM. Assessment of a method to characterize antibody selectivity and specificity for use in immunoprecipitation. Nat Methods. 2015 Aug; 12(8):725-31. View in: PubMed

  49. Nocula-Lugowska M, Lugowski M, Salgia R, Kossiakoff AA. Engineering Synthetic Antibody Inhibitors Specific for LD2 or LD4 Motifs of Paxillin. J Mol Biol. 2015 Jul 31; 427(15):2532-2547. View in: PubMed

  50. Dominik PK, Kossiakoff AA. Phage display selections for affinity reagents to membrane proteins in nanodiscs. Methods Enzymol. 2015; 557:219-45. View in: PubMed

  51. Mateja A, Paduch M, Chang HY, Szydlowska A, Kossiakoff AA, Hegde RS, Keenan RJ. Protein targeting. Structure of the Get3 targeting factor in complex with its membrane protein cargo. Science. 2015 Mar 06; 347(6226):1152-5. View in: PubMed

  52. Stuwe T, Correia AR, Lin DH, Paduch M, Lu VT, Kossiakoff AA, Hoelz A. Nuclear pores. Architecture of the nuclear pore complex coat. Science. 2015 Mar 06; 347(6226):1148-52. View in: PubMed

  53. Miersch S, Li Z, Hanna R, McLaughlin ME, Hornsby M, Matsuguchi T, Paduch M, Sääf A, Wells J, Koide S, Kossiakoff A, Sidhu SS. Scalable high throughput selection from phage-displayed synthetic antibody libraries. J Vis Exp. 2015 Jan 17; (95):51492. View in: PubMed

  54. Rizk SS, Kouadio JL, Szymborska A, Duguid EM, Mukherjee S, Zheng J, Clevenger CV, Kossiakoff AA. Engineering synthetic antibody binders for allosteric inhibition of prolactin receptor signaling. Cell Commun Signal. 2015 Jan 15; 13:1. View in: PubMed

  55. Bailey LJ, Sheehy KM, Hoey RJ, Schaefer ZP, Ura M, Kossiakoff AA. Applications for an engineered Protein-G variant with a pH controllable affinity to antibody fragments. J Immunol Methods. 2014 Dec 15; 415:24-30. View in: PubMed

  56. Welch BD, Paduch M, Leser GP, Bergman Z, Kors CA, Paterson RG, Jardetzky TS, Kossiakoff AA, Lamb RA. Probing the functions of the paramyxovirus glycoproteins F and HN with a panel of synthetic antibodies. J Virol. 2014 Oct; 88(20):11713-25. View in: PubMed

  57. Shukla AK, Westfield GH, Xiao K, Reis RI, Huang LY, Tripathi-Shukla P, Qian J, Li S, Blanc A, Oleskie AN, Dosey AM, Su M, Liang CR, Gu LL, Shan JM, Chen X, Hanna R, Choi M, Yao XJ, Klink BU, Kahsai AW, Sidhu SS, Koide S, Penczek PA, Kossiakoff AA, Woods VL, Kobilka BK, Skiniotis G, Lefkowitz RJ. Visualization of arrestin recruitment by a G-protein-coupled receptor. Nature. 2014 08 14; 512(7513):218-222. View in: PubMed

  58. Marcon E, Ni Z, Pu S, Turinsky AL, Trimble SS, Olsen JB, Silverman-Gavrila R, Silverman-Gavrila L, Phanse S, Guo H, Zhong G, Guo X, Young P, Bailey S, Roudeva D, Zhao D, Hewel J, Li J, Gräslund S, Paduch M, Kossiakoff AA, Lupien M, Emili A, Wodak SJ, Greenblatt J. Human-chromatin-related protein interactions identify a demethylase complex required for chromosome segregation. Cell Rep. 2014 Jul 10; 8(1):297-310. View in: PubMed

  59. Wells JA, Kossiakoff AA. Cell biology. New tricks for an old dimer. Science. 2014 May 16; 344(6185):703-4. View in: PubMed

  60. Li Q, Wanderling S, Paduch M, Medovoy D, Singharoy A, McGreevy R, Villalba-Galea CA, Hulse RE, Roux B, Schulten K, Kossiakoff A, Perozo E. Structural mechanism of voltage-dependent gating in an isolated voltage-sensing domain. Nat Struct Mol Biol. 2014 Mar; 21(3):244-52. View in: PubMed

  61. Shukla AK, Manglik A, Kruse AC, Xiao K, Reis RI, Tseng WC, Staus DP, Hilger D, Uysal S, Huang LY, Paduch M, Tripathi-Shukla P, Koide A, Koide S, Weis WI, Kossiakoff AA, Kobilka BK, Lefkowitz RJ. Structure of active ß-arrestin-1 bound to a G-protein-coupled receptor phosphopeptide. Nature. 2013 May 02; 497(7447):137-41. View in: PubMed

  62. Paduch M, Koide A, Uysal S, Rizk SS, Koide S, Kossiakoff AA. Generating conformation-specific synthetic antibodies to trap proteins in selected functional states. Methods. 2013 Mar 15; 60(1):3-14. View in: PubMed

  63. Rizk SS, Misiura A, Paduch M, Kossiakoff AA. Substance P derivatives as versatile tools for specific delivery of various types of biomolecular cargo. Bioconjug Chem. 2012 Jan 18; 23(1):42-6. View in: PubMed

  64. Uysal S, Cuello LG, Cortes DM, Koide S, Kossiakoff AA, Perozo E. Mechanism of activation gating in the full-length KcsA K+ channel. Proc Natl Acad Sci U S A. 2011 Jul 19; 108(29):11896-9. View in: PubMed

  65. Rizk SS, Paduch M, Heithaus JH, Duguid EM, Sandstrom A, Kossiakoff AA. Allosteric control of ligand-binding affinity using engineered conformation-specific effector proteins. Nat Struct Mol Biol. 2011 Apr; 18(4):437-42. View in: PubMed

  66. Koldobskaya Y, Duguid EM, Shechner DM, Suslov NB, Ye J, Sidhu SS, Bartel DP, Koide S, Kossiakoff AA, Piccirilli JA. A portable RNA sequence whose recognition by a synthetic antibody facilitates structural determination. Nat Struct Mol Biol. 2011 Jan; 18(1):100-6. View in: PubMed

  67. Brawley CM, Uysal S, Kossiakoff AA, Rock RS. Characterization of engineered actin binding proteins that control filament assembly and structure. PLoS One. 2010 Nov 12; 5(11):e13960. View in: PubMed

  68. Kossiakoff AA, Rizk S. Keeping signaling in check. Structure. 2010 Mar 10; 18(3):275-6. View in: PubMed

  69. Bang D, Tereshko V, Kossiakoff AA, Kent SB. Role of a salt bridge in the model protein crambin explored by chemical protein synthesis: X-ray structure of a unique protein analogue, [V15A]crambin-alpha-carboxamide. Mol Biosyst. 2009 Jul; 5(7):750-6. View in: PubMed

  70. Rizk SS, Luchniak A, Uysal S, Brawley CM, Rock RS, Kossiakoff AA. An engineered substance P variant for receptor-mediated delivery of synthetic antibodies into tumor cells. Proc Natl Acad Sci U S A. 2009 Jul 07; 106(27):11011-5. View in: PubMed

  71. Mandal K, Pentelute BL, Tereshko V, Thammavongsa V, Schneewind O, Kossiakoff AA, Kent SB. Racemic crystallography of synthetic protein enantiomers used to determine the X-ray structure of plectasin by direct methods. Protein Sci. 2009 Jun; 18(6):1146-54. View in: PubMed

  72. Uysal S, Vásquez V, Tereshko V, Esaki K, Fellouse FA, Sidhu SS, Koide S, Perozo E, Kossiakoff A. Crystal structure of full-length KcsA in its closed conformation. Proc Natl Acad Sci U S A. 2009 Apr 21; 106(16):6644-9. View in: PubMed

  73. Horn JR, Sosnick TR, Kossiakoff AA. Principal determinants leading to transition state formation of a protein-protein complex, orientation trumps side-chain interactions. Proc Natl Acad Sci U S A. 2009 Feb 24; 106(8):2559-64. View in: PubMed

  74. Mandal K, Pentelute BL, Tereshko V, Kossiakoff AA, Kent SB. X-ray structure of native scorpion toxin BmBKTx1 by racemic protein crystallography using direct methods. J Am Chem Soc. 2009 Feb 04; 131(4):1362-3. View in: PubMed

  75. Kossiakoff AA, Koide S. Understanding mechanisms governing protein-protein interactions from synthetic binding interfaces. Curr Opin Struct Biol. 2008 Aug; 18(4):499-506. View in: PubMed

  76. Pentelute BL, Gates ZP, Tereshko V, Dashnau JL, Vanderkooi JM, Kossiakoff AA, Kent SB. X-ray structure of snow flea antifreeze protein determined by racemic crystallization of synthetic protein enantiomers. J Am Chem Soc. 2008 Jul 30; 130(30):9695-701. View in: PubMed

  77. Tereshko V, Uysal S, Koide A, Margalef K, Koide S, Kossiakoff AA. Toward chaperone-assisted crystallography: protein engineering enhancement of crystal packing and X-ray phasing capabilities of a camelid single-domain antibody (VHH) scaffold. Protein Sci. 2008 Jul; 17(7):1175-87. View in: PubMed

  78. Qiu Y, Zhang R, Binkowski TA, Tereshko V, Joachimiak A, Kossiakoff A. The 1.38 A crystal structure of DmsD protein from Salmonella typhimurium, a proofreading chaperone on the Tat pathway. Proteins. 2008 May 01; 71(2):525-33. View in: PubMed

  79. Ye JD, Tereshko V, Frederiksen JK, Koide A, Fellouse FA, Sidhu SS, Koide S, Kossiakoff AA, Piccirilli JA. Synthetic antibodies for specific recognition and crystallization of structured RNA. Proc Natl Acad Sci U S A. 2008 Jan 08; 105(1):82-7. View in: PubMed

  80. Koide A, Tereshko V, Uysal S, Margalef K, Kossiakoff AA, Koide S. Exploring the capacity of minimalist protein interfaces: interface energetics and affinity maturation to picomolar KD of a single-domain antibody with a flat paratope. J Mol Biol. 2007 Nov 02; 373(4):941-53. View in: PubMed

  81. Fellouse FA, Esaki K, Birtalan S, Raptis D, Cancasci VJ, Koide A, Jhurani P, Vasser M, Wiesmann C, Kossiakoff AA, Koide S, Sidhu SS. High-throughput generation of synthetic antibodies from highly functional minimalist phage-displayed libraries. J Mol Biol. 2007 Nov 02; 373(4):924-40. View in: PubMed

  82. Sidhu SS, Kossiakoff AA. Exploring and designing protein function with restricted diversity. Curr Opin Chem Biol. 2007 Jun; 11(3):347-54. View in: PubMed

  83. Gerdts CJ, Tereshko V, Yadav MK, Dementieva I, Collart F, Joachimiak A, Stevens RC, Kuhn P, Kossiakoff A, Ismagilov RF. Time-controlled microfluidic seeding in nL-volume droplets to separate nucleation and growth stages of protein crystallization. Angew Chem Int Ed Engl. 2006 Dec 11; 45(48):8156-60. View in: PubMed

  84. Horn JR, Kraybill B, Petro EJ, Coales SJ, Morrow JA, Hamuro Y, Kossiakoff AA. The role of protein dynamics in increasing binding affinity for an engineered protein-protein interaction established by H/D exchange mass spectrometry. Biochemistry. 2006 Jul 18; 45(28):8488-98. View in: PubMed

  85. Pál G, Kouadio JK, Artis DR, Kossiakoff AA, Sidhu SS. Comprehensive and quantitative mapping of energy landscapes for protein-protein interactions by rapid combinatorial scanning. J Biol Chem. 2006 Aug 04; 281(31):22378-22385. View in: PubMed

  86. Rizvi SA, Tereshko V, Kossiakoff AA, Kozmin SA. Structure of bistramide A-actin complex at a 1.35 angstroms resolution. J Am Chem Soc. 2006 Mar 29; 128(12):3882-3. View in: PubMed

  87. Walsh ST, Kossiakoff AA. Crystal structure and site 1 binding energetics of human placental lactogen. J Mol Biol. 2006 May 05; 358(3):773-84. View in: PubMed

  88. Bang D, Gribenko AV, Tereshko V, Kossiakoff AA, Kent SB, Makhatadze GI. Dissecting the energetics of protein alpha-helix C-cap termination through chemical protein synthesis. Nat Chem Biol. 2006 Mar; 2(3):139-43. View in: PubMed

  89. Qiu Y, Tereshko V, Kim Y, Zhang R, Collart F, Yousef M, Kossiakoff A, Joachimiak A. The crystal structure of Aq_328 from the hyperthermophilic bacteria Aquifex aeolicus shows an ancestral histone fold. Proteins. 2006 Jan 01; 62(1):8-16. View in: PubMed

  90. Pál G, Fong SY, Kossiakoff AA, Sidhu SS. Alternative views of functional protein binding epitopes obtained by combinatorial shotgun scanning mutagenesis. Protein Sci. 2005 Sep; 14(9):2405-13. View in: PubMed

  91. Kouadio JL, Horn JR, Pal G, Kossiakoff AA. Shotgun alanine scanning shows that growth hormone can bind productively to its receptor through a drastically minimized interface. J Biol Chem. 2005 Jul 08; 280(27):25524-32. View in: PubMed

  92. Bang D, Makhatadze GI, Tereshko V, Kossiakoff AA, Kent SB. Total chemical synthesis and X-ray crystal structure of a protein diastereomer: [D-Gln 35]ubiquitin. Angew Chem Int Ed Engl. 2005 Jun 20; 44(25):3852-6. View in: PubMed

  93. Pál G, Ultsch MH, Clark KP, Currell B, Kossiakoff AA, Sidhu SS. Intramolecular cooperativity in a protein binding site assessed by combinatorial shotgun scanning mutagenesis. J Mol Biol. 2005 Apr 01; 347(3):489-94. View in: PubMed

  94. Gopal B, Madan LL, Betz SF, Kossiakoff AA. The crystal structure of a quercetin 2,3-dioxygenase from Bacillus subtilis suggests modulation of enzyme activity by a change in the metal ion at the active site(s). Biochemistry. 2005 Jan 11; 44(1):193-201. View in: PubMed

  95. Walsh ST, Sylvester JE, Kossiakoff AA. The high- and low-affinity receptor binding sites of growth hormone are allosterically coupled. Proc Natl Acad Sci U S A. 2004 Dec 07; 101(49):17078-83. View in: PubMed

  96. Kossiakoff AA. The structural basis for biological signaling, regulation, and specificity in the growth hormone-prolactin system of hormones and receptors. Adv Protein Chem. 2004; 68:147-69. View in: PubMed

  97. Bernat B, Sun M, Dwyer M, Feldkamp M, Kossiakoff AA. Dissecting the binding energy epitope of a high-affinity variant of human growth hormone: cooperative and additive effects from combining mutations from independently selected phage display mutagenesis libraries. Biochemistry. 2004 May 25; 43(20):6076-84. View in: PubMed

  98. Pal G, Kossiakoff AA, Sidhu SS. The functional binding epitope of a high affinity variant of human growth hormone mapped by shotgun alanine-scanning mutagenesis: insights into the mechanisms responsible for improved affinity. J Mol Biol. 2003 Sep 05; 332(1):195-204. View in: PubMed

  99. Walsh ST, Jevitts LM, Sylvester JE, Kossiakoff AA. Site2 binding energetics of the regulatory step of growth hormone-induced receptor homodimerization. Protein Sci. 2003 Sep; 12(9):1960-70. View in: PubMed

  100. Pál G, Santamaria F, Kossiakoff AA, Lu W. The first semi-synthetic serine protease made by native chemical ligation. Protein Expr Purif. 2003 Jun; 29(2):185-92. View in: PubMed

  101. Bernat B, Pal G, Sun M, Kossiakoff AA. Determination of the energetics governing the regulatory step in growth hormone-induced receptor homodimerization. Proc Natl Acad Sci U S A. 2003 Feb 04; 100(3):952-7. View in: PubMed

  102. Yi S, Bernat B, Pál G, Kossiakoff A, Li WH. Functional promiscuity of squirrel monkey growth hormone receptor toward both primate and nonprimate growth hormones. Mol Biol Evol. 2002 Jul; 19(7):1083-92. View in: PubMed

  103. Schiffer C, Ultsch M, Walsh S, Somers W, de Vos AM, Kossiakoff A. Structure of a phage display-derived variant of human growth hormone complexed to two copies of the extracellular domain of its receptor: evidence for strong structural coupling between receptor binding sites. J Mol Biol. 2002 Feb 15; 316(2):277-89. View in: PubMed

  104. Dwyer JJ, Dwyer MA, Kossiakoff AA. High affinity RNase S-peptide variants obtained by phage display have a novel "hot-spot" of binding energy. Biochemistry. 2001 Nov 13; 40(45):13491-500. View in: PubMed

  105. Randal M, Kossiakoff AA. The structure and activity of a monomeric interferon-gamma:alpha-chain receptor signaling complex. Structure. 2001 Feb 07; 9(2):155-63. View in: PubMed

  106. Elkins PA, Christinger HW, Sandowski Y, Sakal E, Gertler A, de Vos AM, Kossiakoff AA. Ternary complex between placental lactogen and the extracellular domain of the prolactin receptor. Nat Struct Biol. 2000 Sep; 7(9):808-15. View in: PubMed

  107. Dwyer MA, Lu W, Dwyer JJ, Kossiakoff AA. Biosynthetic phage display: a novel protein engineering tool combining chemical and genetic diversity. Chem Biol. 2000 Apr; 7(4):263-74. View in: PubMed

  108. Lu WY, Starovasnik MA, Dwyer JJ, Kossiakoff AA, Kent SB, Lu W. Deciphering the role of the electrostatic interactions involving Gly70 in eglin C by total chemical protein synthesis. Biochemistry. 2000 Apr 04; 39(13):3575-84. View in: PubMed

  109. Randal M, Kossiakoff AA. The 2.0 A structure of bovine interferon-gamma; assessment of the structural differences between species. Acta Crystallogr D Biol Crystallogr. 2000 Jan; 56(Pt 1):14-24. View in: PubMed

  110. Lu W, Randal M, Kossiakoff A, Kent SB. Probing intermolecular backbone H-bonding in serine proteinase-protein inhibitor complexes. Chem Biol. 1999 Jul; 6(7):419-27. View in: PubMed

  111. Christinger HW, Elkins PA, Sandowski Y, Sakal E, Gertler A, Kossiakoff AA, de Vos AM. Crystallization of ovine placental lactogen in a 1:2 complex with the extracellular domain of the rat prolactin receptor. Acta Crystallogr D Biol Crystallogr. 1998 Nov 01; 54(Pt 6 Pt 2):1408-11. View in: PubMed

  112. Kossiakoff AA, De Vos AM. Structural basis for cytokine hormone-receptor recognition and receptor activation. Adv Protein Chem. 1998; 52:67-108. View in: PubMed

  113. Randal M, Kossiakoff AA. Crystallization and preliminary X-ray analysis of a 1:1 complex between a designed monomeric interferon-gamma and its soluble receptor. Protein Sci. 1998 Apr; 7(4):1057-60. View in: PubMed

  114. Scheidig AJ, Hynes TR, Pelletier LA, Wells JA, Kossiakoff AA. Crystal structures of bovine chymotrypsin and trypsin complexed to the inhibitor domain of Alzheimer's amyloid beta-protein precursor (APPI) and basic pancreatic trypsin inhibitor (BPTI): engineering of inhibitors with altered specificities. Protein Sci. 1997 Sep; 6(9):1806-24. View in: PubMed

  115. McDowell RS, Kossiakoff AA. Hydroxyl and water molecule orientations in trypsin: comparison to molecular dynamic structures. Basic Life Sci. 1996; 64:273-87. View in: PubMed

  116. Kossiakoff AA, Hynes T, de Vos A. Molecular recognition in biological systems: from activation to inhibition. Biochem Soc Trans. 1993 Aug; 21 ( Pt 3)(3):614-8. View in: PubMed

  117. Ultsch MH, Somers W, Kossiakoff AA, de Vos AM. The crystal structure of affinity-matured human growth hormone at 2 A resolution. J Mol Biol. 1994 Feb 11; 236(1):286-99. View in: PubMed

  118. Eigenbrot C, Randal M, Presta L, Carter P, Kossiakoff AA. X-ray structures of the antigen-binding domains from three variants of humanized anti-p185HER2 antibody 4D5 and comparison with molecular modeling. J Mol Biol. 1993 Feb 20; 229(4):969-95. View in: PubMed

  119. Somers W, Ultsch M, De Vos AM, Kossiakoff AA. The X-ray structure of a growth hormone-prolactin receptor complex. Nature. 1994 Dec 01; 372(6505):478-81. View in: PubMed

  120. Kossiakoff AA, Somers W, Ultsch M, Andow K, Muller YA, De Vos AM. Comparison of the intermediate complexes of human growth hormone bound to the human growth hormone and prolactin receptors. Protein Sci. 1994 Oct; 3(10):1697-705. View in: PubMed

  121. Gamble TR, Clauser KR, Kossiakoff AA. The production and X-ray structure determination of perdeuterated Staphylococcal nuclease. Biophys Chem. 1994 Dec; 53(1-2):15-25. View in: PubMed

  122. Kossiakoff AA. Structure of the growth hormone-receptor complex and mechanism of receptor signaling. J Nucl Med. 1995 Jun; 36(6 Suppl):14S-16S. View in: PubMed

  123. McDowell RS, Kossiakoff AA. A comparison of neutron diffraction and molecular dynamics structures: hydroxyl group and water molecule orientations in trypsin. J Mol Biol. 1995 Jul 21; 250(4):553-70. View in: PubMed

  124. Kossiakoff AA, Spencer SA. Neutron diffraction identifies His 57 as the catalytic base in trypsin. Nature. 1980 Nov 27; 288(5789):414-6. View in: PubMed

  125. Kossiakoff AA. Protein dynamics investigated by the neutron diffraction-hydrogen exchange technique. Nature. 1982 Apr 22; 296(5859):713-21. View in: PubMed

  126. Kossiakoff AA, Spencer SA. Direct determination of the protonation states of aspartic acid-102 and histidine-57 in the tetrahedral intermediate of the serine proteases: neutron structure of trypsin. Biochemistry. 1981 Oct 27; 20(22):6462-74. View in: PubMed

  127. Kossiakoff AA. Use of the neutron diffraction--H/D exchange technique to determine the conformational dynamics of trypsin. Basic Life Sci. 1984; 27:281-304. View in: PubMed

  128. Kossiakoff AA, Shteyn S. Effect of protein packing structure on side-chain methyl rotor conformations. Nature. 1984 Oct 11-17; 311(5986):582-3. View in: PubMed

  129. Kossiakoff AA. Neutron protein crystallography: advances in methods and applications. Annu Rev Biophys Bioeng. 1983; 12:159-82. View in: PubMed

  130. Kossiakoff AA, Spencer SA. Automated peak fitting procedure for processing data from an area detector and its application to the neutron structure of trypsin. Methods Enzymol. 1985; 114:530-51. View in: PubMed

  131. Kossiakoff AA. The application of neutron crystallography to the study of dynamic and and hydration properties of proteins. Annu Rev Biochem. 1985; 54:1195-227. View in: PubMed

  132. Kossiakoff AA. Protein dynamics investigated by neutron diffraction. Methods Enzymol. 1986; 131:433-47. View in: PubMed

  133. Kossiakoff AA. Tertiary structure is a principal determinant to protein deamidation. Science. 1988 Apr 08; 240(4849):191-4. View in: PubMed

  134. Bott R, Ultsch M, Kossiakoff A, Graycar T, Katz B, Power S. The three-dimensional structure of Bacillus amyloliquefaciens subtilisin at 1.8 A and an analysis of the structural consequences of peroxide inactivation. J Biol Chem. 1988 Jun 05; 263(16):7895-906. View in: PubMed

  135. Katz BA, Kossiakoff A. The crystallographically determined structures of atypical strained disulfides engineered into subtilisin. J Biol Chem. 1986 Nov 25; 261(33):15480-5. View in: PubMed

  136. Kossiakoff AA. The use of neutrons to show how proteins work. Basic Life Sci. 1988; 46:63-78. View in: PubMed

  137. Shpungin J, Kossiakoff AA. A method of solvent structure analysis for proteins using D2O-H2O neutron difference maps. Methods Enzymol. 1986; 127:329-42. View in: PubMed

  138. Kossiakoff AA, Shpungin J, Sintchak MD. Hydroxyl hydrogen conformations in trypsin determined by the neutron diffraction solvent difference map method: relative importance of steric and electrostatic factors in defining hydrogen-bonding geometries. Proc Natl Acad Sci U S A. 1990 Jun; 87(12):4468-72. View in: PubMed

  139. Katz B, Kossiakoff AA. Crystal structures of subtilisin BPN' variants containing disulfide bonds and cavities: concerted structural rearrangements induced by mutagenesis. Proteins. 1990; 7(4):343-57. View in: PubMed

  140. Hynes TR, Randal M, Kennedy LA, Eigenbrot C, Kossiakoff AA. X-ray crystal structure of the protease inhibitor domain of Alzheimer's amyloid beta-protein precursor. Biochemistry. 1990 Oct 30; 29(43):10018-22. View in: PubMed

  141. Abrahmsén L, Tom J, Burnier J, Butcher KA, Kossiakoff A, Wells JA. Engineering subtilisin and its substrates for efficient ligation of peptide bonds in aqueous solution. Biochemistry. 1991 Apr 30; 30(17):4151-9. View in: PubMed

  142. Kossiakoff AA, Ultsch M, White S, Eigenbrot C. Neutron structure of subtilisin BPN': effects of chemical environment on hydrogen-bonding geometries and the pattern of hydrogen-deuterium exchange in secondary structure elements. Biochemistry. 1991 Feb 05; 30(5):1211-21. View in: PubMed

  143. Ultsch M, de Vos AM, Kossiakoff AA. Crystals of the complex between human growth hormone and the extracellular domain of its receptor. J Mol Biol. 1991 Dec 20; 222(4):865-8. View in: PubMed

  144. Eigenbrot C, Randal M, Kossiakoff AA. Structural effects induced by removal of a disulfide-bridge: the X-ray structure of the C30A/C51A mutant of basic pancreatic trypsin inhibitor at 1.6 A. Protein Eng. 1990 Jul; 3(7):591-8. View in: PubMed

  145. Eigenbrot C, Randal M, Quan C, Burnier J, O'Connell L, Rinderknecht E, Kossiakoff AA. X-ray structure of human relaxin at 1.5 A. Comparison to insulin and implications for receptor binding determinants. J Mol Biol. 1991 Sep 05; 221(1):15-21. View in: PubMed

  146. Kossiakoff AA, Sintchak MD, Shpungin J, Presta LG. Analysis of solvent structure in proteins using neutron D2O-H2O solvent maps: pattern of primary and secondary hydration of trypsin. Proteins. 1992 Mar; 12(3):223-36. View in: PubMed

  147. Finer-Moore JS, Kossiakoff AA, Hurley JH, Earnest T, Stroud RM. Solvent structure in crystals of trypsin determined by X-ray and neutron diffraction. Proteins. 1992 Mar; 12(3):203-22. View in: PubMed

  148. de Vos AM, Ultsch M, Kossiakoff AA. Human growth hormone and extracellular domain of its receptor: crystal structure of the complex. Science. 1992 Jan 17; 255(5042):306-12. View in: PubMed

  149. Eigenbrot C, Randal M, Kossiakoff AA. Structural effects induced by mutagenesis affected by crystal packing factors: the structure of a 30-51 disulfide mutant of basic pancreatic trypsin inhibitor. Proteins. 1992 Sep; 14(1):75-87. View in: PubMed

  150. Kossiakoff AA, Randal M, Guenot J, Eigenbrot C. Variability of conformations at crystal contacts in BPTI represent true low-energy structures: correspondence among lattice packing and molecular dynamics structures. Proteins. 1992 Sep; 14(1):65-74. View in: PubMed

  151. Eigenbrot C, Kossiakoff AA. Structural consequences of mutation. Curr Opin Biotechnol. 1992 Aug; 3(4):333-7. View in: PubMed

  152. de Vos AM, Ultsch MH, Kelley RF, Padmanabhan K, Tulinsky A, Westbrook ML, Kossiakoff AA. Crystal structure of the kringle 2 domain of tissue plasminogen activator at 2.4-A resolution. Biochemistry. 1992 Jan 14; 31(1):270-9. View in: PubMed

  153. Kossiakoff AA, Chambers JL, Kay LM, Stroud RM. Structure of bovine trypsinogen at 1.9 A resolution. Biochemistry. 1977 Feb 22; 16(4):654-64. View in: PubMed

  154. Stroud RM, Kossiakoff AA, Chambers JL. Mechanisms of zymogen activation. Annu Rev Biophys Bioeng. 1977; 6:177-93. View in: PubMed