Robert J. Keenan

Research Summary
We study the molecular mechanisms underlying membrane protein biogenesis and quality control using biochemical, structural and cell biology approaches.
Membrane protein biogenesis, Membrane protein quality control, Structural biology, Biochemical reconstitution, Cell biology
  • Bates College, Lewiston, ME, BS Biology and Chemistry 06/1990
  • UCSF, San Francisco, CA, PHD Biochemistry and Biophysics 05/1998
  • UCSF, San Francisco, CA, Postdoc Biochemistry and Biophysics 09/1999
Biosciences Graduate Program Association
  1. Smalinskaite L, Kim MK, Lewis AJO, Keenan RJ, Hegde RS. Mechanism of an intramembrane chaperone for multipass membrane proteins. Nature. 2022 11; 611(7934):161-166. View in: PubMed

  2. Sundaram A, Yamsek M, Zhong F, Hooda Y, Hegde RS, Keenan RJ. Substrate-driven assembly of a translocon for multipass membrane proteins. Nature. 2022 11; 611(7934):167-172. View in: PubMed

  3. Hegde RS, Keenan RJ. The mechanisms of integral membrane protein biogenesis. Nat Rev Mol Cell Biol. 2022 02; 23(2):107-124. View in: PubMed

  4. McGilvray PT, Anghel SA, Sundaram A, Zhong F, Trnka MJ, Fuller JR, Hu H, Burlingame AL, Keenan RJ. An ER translocon for multi-pass membrane protein biogenesis. Elife. 2020 08 21; 9. View in: PubMed

  5. O'Donnell JP, Phillips BP, Yagita Y, Juszkiewicz S, Wagner A, Malinverni D, Keenan RJ, Miller EA, Hegde RS. The architecture of EMC reveals a path for membrane protein insertion. Elife. 2020 05 27; 9. View in: PubMed

  6. Mateja A, Keenan RJ. A structural perspective on tail-anchored protein biogenesis by the GET pathway. Curr Opin Struct Biol. 2018 08; 51:195-202. View in: PubMed

  7. Anghel SA, McGilvray PT, Hegde RS, Keenan RJ. Identification of Oxa1 Homologs Operating in the Eukaryotic Endoplasmic Reticulum. Cell Rep. 2017 12 26; 21(13):3708-3716. View in: PubMed

  8. Zalisko BE, Chan C, Denic V, Rock RS, Keenan RJ. Tail-Anchored Protein Insertion by a Single Get1/2 Heterodimer. Cell Rep. 2017 Sep 05; 20(10):2287-2293. View in: PubMed

  9. Wohlever ML, Mateja A, McGilvray PT, Day KJ, Keenan RJ. Msp1 Is a Membrane Protein Dislocase for Tail-Anchored Proteins. Mol Cell. 2017 Jul 20; 67(2):194-202.e6. View in: PubMed

  10. Srivastava R, Zalisko BE, Keenan RJ, Howell SH. The GET System Inserts the Tail-Anchored Protein, SYP72, into Endoplasmic Reticulum Membranes. Plant Physiol. 2017 02; 173(2):1137-1145. View in: PubMed

  11. Itakura E, Zavodszky E, Shao S, Wohlever ML, Keenan RJ, Hegde RS. Ubiquilins Chaperone and Triage Mitochondrial Membrane Proteins for Degradation. Mol Cell. 2016 07 07; 63(1):21-33. View in: PubMed

  12. Meyer PA, Socias S, Key J, Ransey E, Tjon EC, Buschiazzo A, Lei M, Botka C, Withrow J, Neau D, Rajashankar K, Anderson KS, Baxter RH, Blacklow SC, Boggon TJ, Bonvin AM, Borek D, Brett TJ, Caflisch A, Chang CI, Chazin WJ, Corbett KD, Cosgrove MS, Crosson S, Dhe-Paganon S, Di Cera E, Drennan CL, Eck MJ, Eichman BF, Fan QR, Ferré-D'Amaré AR, Fromme JC, Garcia KC, Gaudet R, Gong P, Harrison SC, Heldwein EE, Jia Z, Keenan RJ, Kruse AC, Kvansakul M, McLellan JS, Modis Y, Nam Y, Otwinowski Z, Pai EF, Pereira PJ, Petosa C, Raman CS, Rapoport TA, Roll-Mecak A, Rosen MK, Rudenko G, Schlessinger J, Schwartz TU, Shamoo Y, Sondermann H, Tao YJ, Tolia NH, Tsodikov OV, Westover KD, Wu H, Foster I, Fraser JS, Maia FR, Gonen T, Kirchhausen T, Diederichs K, Crosas M, Sliz P. Data publication with the structural biology data grid supports live analysis. Nat Commun. 2016 Mar 07; 7:10882. View in: PubMed

  13. 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

  14. Gomes AC, Kordala AJ, Strack R, Wang X, Geslain R, Delaney K, Clark WC, Keenan R, Pan T. A dual fluorescent reporter for the investigation of methionine mistranslation in live cells. RNA. 2016 Mar; 22(3):467-76. View in: PubMed

  15. 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

  16. 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

  17. Bestul AJ, Christensen JR, Grzegorzewska AP, Burke TA, Sees JA, Carroll RT, Sirotkin V, Keenan RJ, Kovar DR. Fission yeast profilin is tailored to facilitate actin assembly by the cytokinesis formin Cdc12. Mol Biol Cell. 2015 Jan 15; 26(2):283-93. View in: PubMed

  18. Hegde RS, Keenan RJ. Tail-anchored membrane protein insertion into the endoplasmic reticulum. Nat Rev Mol Cell Biol. 2011 Nov 16; 12(12):787-98. View in: PubMed

  19. Mariappan M, Mateja A, Dobosz M, Bove E, Hegde RS, Keenan RJ. The mechanism of membrane-associated steps in tail-anchored protein insertion. Nature. 2011 Aug 24; 477(7362):61-6. View in: PubMed

  20. Sherrill J, Mariappan M, Dominik P, Hegde RS, Keenan RJ. A conserved archaeal pathway for tail-anchored membrane protein insertion. Traffic. 2011 Sep; 12(9):1119-23. View in: PubMed

  21. Strack RL, Keenan RJ, Glick BS. Noncytotoxic DsRed derivatives for whole-cell labeling. Methods Mol Biol. 2011; 699:355-70. View in: PubMed

  22. Mariappan M, Li X, Stefanovic S, Sharma A, Mateja A, Keenan RJ, Hegde RS. A ribosome-associating factor chaperones tail-anchored membrane proteins. Nature. 2010 Aug 26; 466(7310):1120-4. View in: PubMed

  23. Strack RL, Strongin DE, Mets L, Glick BS, Keenan RJ. Chromophore formation in DsRed occurs by a branched pathway. J Am Chem Soc. 2010 Jun 23; 132(24):8496-505. View in: PubMed

  24. Mateja A, Szlachcic A, Downing ME, Dobosz M, Mariappan M, Hegde RS, Keenan RJ. The structural basis of tail-anchored membrane protein recognition by Get3. Nature. 2009 Sep 17; 461(7262):361-6. View in: PubMed

  25. Strack RL, Hein B, Bhattacharyya D, Hell SW, Keenan RJ, Glick BS. A rapidly maturing far-red derivative of DsRed-Express2 for whole-cell labeling. Biochemistry. 2009 Sep 08; 48(35):8279-81. View in: PubMed

  26. Strack RL, Bhattacharyya D, Glick BS, Keenan RJ. Noncytotoxic orange and red/green derivatives of DsRed-Express2 for whole-cell labeling. BMC Biotechnol. 2009 Apr 03; 9:32. View in: PubMed

  27. Strack RL, Strongin DE, Bhattacharyya D, Tao W, Berman A, Broxmeyer HE, Keenan RJ, Glick BS. A noncytotoxic DsRed variant for whole-cell labeling. Nat Methods. 2008 Nov; 5(11):955-7. View in: PubMed

  28. Schnitzler CE, Keenan RJ, McCord R, Matysik A, Christianson LM, Haddock SH. Spectral diversity of fluorescent proteins from the anthozoan Corynactis californica. Mar Biotechnol (NY). 2008 May-Jun; 10(3):328-42. View in: PubMed

  29. Strongin DE, Bevis B, Khuong N, Downing ME, Strack RL, Sundaram K, Glick BS, Keenan RJ. Structural rearrangements near the chromophore influence the maturation speed and brightness of DsRed variants. Protein Eng Des Sel. 2007 Nov; 20(11):525-34. View in: PubMed

  30. Siehl DL, Castle LA, Gorton R, Keenan RJ. The molecular basis of glyphosate resistance by an optimized microbial acetyltransferase. J Biol Chem. 2007 Apr 13; 282(15):11446-55. View in: PubMed

  31. Yuan L, Kurek I, English J, Keenan R. Laboratory-directed protein evolution. Microbiol Mol Biol Rev. 2005 Sep; 69(3):373-92. View in: PubMed

  32. Keenan RJ, Siehl DL, Gorton R, Castle LA. DNA shuffling as a tool for protein crystallization. Proc Natl Acad Sci U S A. 2005 Jun 21; 102(25):8887-92. View in: PubMed

  33. Siehl DL, Castle LA, Gorton R, Chen YH, Bertain S, Cho HJ, Keenan R, Liu D, Lassner MW. Evolution of a microbial acetyltransferase for modification of glyphosate: a novel tolerance strategy. Pest Manag Sci. 2005 Mar; 61(3):235-40. View in: PubMed

  34. Keenan RJ, Stemmer WP. Nontransgenic crops from transgenic plants. Nat Biotechnol. 2002 Mar; 20(3):215-6. View in: PubMed

  35. Keenan RJ, Freymann DM, Stroud RM, Walter P. The signal recognition particle. Annu Rev Biochem. 2001; 70:755-75. View in: PubMed

  36. Walter P, Keenan R, Schmitz U. Perspectives: structural biology. SRP--where the RNA and membrane worlds meet. Science. 2000 Feb 18; 287(5456):1212-3. View in: PubMed

  37. Schmitz U, Behrens S, Freymann DM, Keenan RJ, Lukavsky P, Walter P, James TL. Structure of the phylogenetically most conserved domain of SRP RNA. RNA. 1999 Nov; 5(11):1419-29. View in: PubMed

  38. Freymann DM, Keenan RJ, Stroud RM, Walter P. Functional changes in the structure of the SRP GTPase on binding GDP and Mg2+GDP. Nat Struct Biol. 1999 Aug; 6(8):793-801. View in: PubMed

  39. Keenan RJ, Freymann DM, Walter P, Stroud RM. Crystal structure of the signal sequence binding subunit of the signal recognition particle. Cell. 1998 Jul 24; 94(2):181-91. View in: PubMed

  40. Freymann DM, Keenan RJ, Stroud RM, Walter P. Structure of the conserved GTPase domain of the signal recognition particle. Nature. 1997 Jan 23; 385(6614):361-4. View in: PubMed

  41. Schmitz U, Freymann DM, James TL, Keenan RJ, Vinayak R, Walter P. NMR studies of the most conserved RNA domain of the mammalian signal recognition particle (SRP). RNA. 1996 Dec; 2(12):1213-27. View in: PubMed

  42. Rutenber E, Fauman EB, Keenan RJ, Fong S, Furth PS, Ortiz de Montellano PR, Meng E, Kuntz ID, DeCamp DL, Salto R, et al. Structure of a non-peptide inhibitor complexed with HIV-1 protease. Developing a cycle of structure-based drug design. J Biol Chem. 1993 Jul 25; 268(21):15343-6. View in: PubMed