Research Activities
One of our goals is to decipher the molecular mechanisms of synaptic neurotransmitter release by conducting single-molecule/particle reconstitution and imaging experiments, combined with high-resolution structural studies of the synaptic vesicle fusion machinery.
Selected Projects Recent Publications

Primed synaptic fusion complex

SNARE/complexin/synaptotagmin complex

20S complex

NSF/SNAP/SNARE Complex (Cryo-EM Structure)

Reconstitution

Reconstitution of Synaptic Vesicle Fusion

Reconstitution

Single Molecule Studies

 K.I. White, M. Zhao, U.B. Choi, R.A. Pfuetzner, A.T. Brunger. Structural principles of SNARE complex recognition by the AAA+ protein NSF. eLife, e38888. 10.7554/eLife.38888 (2018).

 Choi,U.B., Zhao,M., White,K.I., Pfuetzner,R.A., Esquivies,L., Zhou,Q., Brunger,A.T. (2018). NSF-mediated disassembly of on and off-pathway SNARE complexes and inhibition by complexin. eLife 7, e36497, 10.7554/eLife.36497 (2018).

 A.T.Brunger U.B.Choi, Y.Lai, J.Leitz, Q.Zhou. Molecular Mechanisms of Fast Neurotransmitter Release. Annu. Rev. Biophys. 47, 469–497 (2018).

 A.T.Brunger, J.Leitz, Q.Zhou, U.B.Choi, Ying Lai. Ca2+-triggered synaptic vesicle fusion initiated by release of inhibition. Trends in Cell Biology 28, 631-645 (2018).

 Q.Zhou, P.Zhou, A.L.Wang, D.Wu, M.Zhao, T.C.Sudhof, A.T.Brunger. The primed SNARE-complexin-synaptotagmin complex for neuronal exocytosis. Nature 548, 420-425 (2017).

 Y.Lai, U.B.Choi, J.Leitz, H.J.Rhee, C.Lee, B.Altas, M.Zhao, R.A.Pfuetzner, A.L.Wang, N.Brose, J.Rhee, A.T.Brunger. Molecular mechanisms of synaptic vesicle priming by Munc13 and Munc18. Neuron 95, 591-607 (2017).

 P.Gipson, Y.Fukuda, R.Danev, Y.Lai, D.-H.Chen, W.Baumeister, A.T.Brunger. Morphologies of synaptic protein membrane fusion interfaces. Proc. Natl. Acad. Sci. USA 114, 9110-9115 (2017).

 S.Wang, U.B.Choi, J.Gong, X.Yang, Y.Li, A.L.Wang, X.Yang, A.T.Brunger, C.Ma. Conformational change of syntaxin linker region induced by Munc13s initiates SNARE complex formation in synaptic exocytosis.EMBO J. 36, 816-829 (2017).

Key Publications (out of over 280)

 Q.Zhou, P.Zhou, A.L.Wang, D.Wu, M.Zhao, T.C.Sudhof, A.T.Brunger. The primed SNARE-complexin-synaptotagmin complex for neuronal exocytosis. Nature 548, 420-425 (2017).

 Y.Lai, U.B.Choi, J.Leitz, H.J.Rhee, C.Lee, B.Altas, M.Zhao, R.A.Pfuetzner, A.L.Wang, N.Brose, J.Rhee, A.T.Brunger. Molecular mechanisms of synaptic vesicle priming by Munc13 and Munc18. Neuron 95, 591-607 (2017).

 Q.Zhou, Y.Lai, T.Bacaj, M.Zhao, A.Y.Lyubimov, M.Uervirojnangkoorn, O.B.Zeldin, A.S.Brewster, N.K.Sauter, A.E.Cohen, S.M.Soltis, R.Alonso-Mori, M.Chollet, H.T.Lemke, R.A.Pfuetzner, U.B.Choi, W.I.Weis, J.Diao, T.C.Sudhof, A.T.Brunger, Architecture of the synaptotagmin-SNARE machinery for neuronal exocytosis. Nature 525, 62-67 (2015).

 M.Zhao, S.Wu, Q.Zhou, S.Vivona, D.J.Cipriano, Y.Cheng, A.T.Brunger. Mechanistic insights into the recycling machine of the SNARE complex. Nature 518, 61-67 (2015).

 Y.Lai, J.Diao, D.J.Cipriano, Y.Zhang, R.A.Pfuetzner, M.S.Padolina, A.T.Brunger. Complexin inhibits spontaneous release and synchronizes Ca2+-triggered synaptic vesicle fusion by distinct mechanisms. eLife 3, e03756 (2014).

 J.Diao, J.Burre, S.Vivona, D.J.Cipriano, M.Sharma, M.Kyoung, T.C.Sudhof, A.T.Brunger. Native α-synuclein induces clustering of synaptic-vesicle mimics via binding to phospholipids and synaptobrevin-2/VAMP2. eLife 2, e00592 (2013)

 J.Diao, P.Grob, D.J.Cipriano, M.Kyoung, Y.Zhang, S.Shah, A.Nguyen, M.Padolina, A.Srivastava, M.Vrljic, A.Shah, E.Nogales, S.Chu, A.T.Brunger. Synaptic proteins promote calcium-triggered fusion from point contract to full fusion. eLife 1, e00109 (2012).

 G.F.Schroeder, M.Levitt, A.T.Brunger, Super-resolution biomolecular crystallography with low-resolution data. Nature 464, 1218-1222 (2010).

 M.A.Breidenbach, A.T.Brunger, Substrate recognition strategy for botulinum neurotoxin serotype A, Nature 432 925-929 (2004).

 K. Weninger, M.E. Bowen, S. Chu, and A.T. Brunger, Single molecule studies of SNARE complex assembly reveal parallel and anti-parallel configurations, Proceedings of the National Academy of Sciences USA100, 14800-14805 (2003)

 B. DeLaBarre and A.T. Brunger, Complete Structure of p97/Valosin-Containing Protein Reveals Communication Between Nucleotide Domains, Nature Structural Biology 10, 856-863 (2003).

 R.B.Sutton, D.Fasshauer, R.Jahn, A.T.Brunger. Crystal structure of a SNARE complex involved in synaptic exocytosis at 2.4 A resolution. Nature 395, 347-353 (1998).

 A.T.Brunger, P. D.Adams, G. M.Clore, W.L.DeLano, P.Gros, R.W.Grosse-Kunstleve, J.-S.Jiang, J.Kuszewski, M.Nilges, N.S.Pannu, R.J.Read, L.M.Rice, T.Simonson, G.L.Warren, Crystallography & NMR system (CNS): A new software system for macromolecular structure determination, Acta Cryst. D 54, 905-921 (1998).

 F. T. Burling, W. I. Weis, K. M. Flaherty, and A. T. Brunger, Direct observation of protein solvation and discrete disorder with experimental crystallographic phases, Science 271, 72-77 (1996).

 A.T.Brunger, The free R value: a novel statistical quantity for assessing the accuracy of crystal structures, Nature 355, 472-474 (1992).

 A.T.Brunger, J.Kuriyan, M.Karplus, Crystallographic R factor refinement by molecular dynamics, Science 235, 458-460 (1987).

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