Minglei Zhao

Assistant Professor
Websites
Research Summary
As a structural biology lab, we are interested in understanding the mechanism of molecular machines and their roles in human diseases. Currently we focus on two systems, p97 / ubiquitination system, and vault. p97 is a central hub in cellular protein homeostasis. It is involved in several neurodegenerative diseases, and is also a cancer drug target. We want to gain insights into the molecular architectures of p97 in complex with various cofactor proteins and poly-ubiquitinated substrates. We are investigating the specificity of p97 towards ubiquitin chains with various topologies. Our findings will elucidate the molecular mechanism of human p97. Vault is the largest ribonuclear protein in many eukaryotes including human. It is a membraneless organelle. Despite the fact that vault has been studied for thirty years, its function remains elusive. Overexpression of major vault protein (MVP) correlates with drug resistance in cancer cells. However, the mechanism is completely unknown at the molecular level. We are investigating the structures of vault components and using proteomic and imaging techniques to address the molecular function of vault. There are two major techniques used in the lab: X-ray crystallography and cryo-electron microscopy.
Keywords
AAA+ ATPase, p97, Ubiquitination, Vault RNP Particle
Education
  • Stanford University and Howard Hughes Medical Institute, California, USA, Biophysics and Structural Biology 12/2016
  • University of California Los Angeles, California, USA, Ph.D. Molecular Biology 12/2011
  • Fudan University, Shanghai, China, B.S. Biological Sciences 06/2005
Biosciences Graduate Program Association
Publications
  1. Li J, Xie Y, Cornelius S, Jiang X, Sando R, Kordon SP, Pan M, Leon K, Südhof TC, Zhao M, Araç D. Alternative splicing controls teneurin-latrophilin interaction and synapse specificity by a shape-shifting mechanism. Nat Commun. 2020 05 01; 11(1):2140. View in: PubMed

  2. Leon K, Cunningham RL, Riback JA, Feldman E, Li J, Sosnick TR, Zhao M, Monk KR, Araç D. Structural basis for adhesion G protein-coupled receptor Gpr126 function. Nat Commun. 2020 01 10; 11(1):194. View in: PubMed

  3. White KI, Zhao M, Choi UB, Pfuetzner RA, Brunger AT. Structural principles of SNARE complex recognition by the AAA+ protein NSF. Elife. 2018 09 10; 7. View in: PubMed

  4. Wang B, Lee J, Li P, Saberi A, Yang H, Liu C, Zhao M, Newmark PA. Stem cell heterogeneity drives the parasitic life cycle of Schistosoma mansoni. Elife. 2018 07 10; 7. View in: PubMed

  5. Choi UB, Zhao M, White KI, Pfuetzner RA, Esquivies L, Zhou Q, Brunger AT. NSF-mediated disassembly of on- and off-pathway SNARE complexes and inhibition by complexin. Elife. 2018 07 09; 7. View in: PubMed

  6. Luo F, Gui X, Zhou H, Gu J, Li Y, Liu X, Zhao M, Li D, Li X, Liu C. Atomic structures of FUS LC domain segments reveal bases for reversible amyloid fibril formation. Nat Struct Mol Biol. 2018 04; 25(4):341-346. View in: PubMed

  7. Zhou Q, Zhou P, Wang AL, Wu D, Zhao M, Südhof TC, Brunger AT. The primed SNARE-complexin-synaptotagmin complex for neuronal exocytosis. Nature. 2017 08 24; 548(7668):420-425. View in: PubMed

  8. Lai Y, Choi UB, Leitz J, Rhee HJ, Lee C, Altas B, Zhao M, Pfuetzner RA, Wang AL, Brose N, Rhee J, Brunger AT. Molecular Mechanisms of Synaptic Vesicle Priming by Munc13 and Munc18. Neuron. 2017 Aug 02; 95(3):591-607.e10. View in: PubMed

  9. Lyubimov AY, Uervirojnangkoorn M, Zeldin OB, Zhou Q, Zhao M, Brewster AS, Michels-Clark T, Holton JM, Sauter NK, Weis WI, Brunger AT. Advances in X-ray free electron laser (XFEL) diffraction data processing applied to the crystal structure of the synaptotagmin-1 / SNARE complex. Elife. 2016 10 12; 5. View in: PubMed

  10. Lai Y, Choi UB, Zhang Y, Zhao M, Pfuetzner RA, Wang AL, Diao J, Brunger AT. N-terminal domain of complexin independently activates calcium-triggered fusion. Proc Natl Acad Sci U S A. 2016 08 09; 113(32):E4698-707. View in: PubMed

  11. Choi UB, Zhao M, Zhang Y, Lai Y, Brunger AT. Complexin induces a conformational change at the membrane-proximal C-terminal end of the SNARE complex. Elife. 2016 06 02; 5. View in: PubMed

  12. Zhao M, Brunger AT. Recent Advances in Deciphering the Structure and Molecular Mechanism of the AAA+ ATPase N-Ethylmaleimide-Sensitive Factor (NSF). J Mol Biol. 2016 05 08; 428(9 Pt B):1912-26. View in: PubMed