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

20S complex

NSF/SNAP/SNARE Complex (Cryo-EM Structure at 7.6 A Resolution)

Synaptotagmin-1/SNARE Complex (click for vesicle fusion animation}

Reconstitution

Reconstitution of Synaptic Vesicle Fusion

Reconstitution

Single Molecule Studies

 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).

 J.Gong, Y.Lai, X.Li, M.Wang, J.Leitz, Y.Hu, Y.Zhang, U.B.Choi, D.Cipriano, R.A.Pfuetzner, T.C.Sudhof, X.Yang, A.T.Brunger, J.Diao (2016). C-terminal domain of mammalian complexin-1 localizes to highly curved membranes. Proc. Natl. Acad. Sci. 113, E7590-E7599 (2016).

 A.Y.Lyubimov, M.Uervirojnangkoorn, O.B.Zeldin, Q.Zhou, M.Zhao, A.S.Brewster, T.Michels-Clark, J.M.Holton, N.K.Sauter, W.I.Weis, and A.T.Brunger (2016). Advances in X-ray free electron laser (XFEL) diffraction data processing applied to the crystal structure of the synaptotagmin-1 / SNARE complex. Elife 5 e18740 (2016).

 D.C.Martinelli, K.S.Chew, A.Rohlmann, M.Y.Lum, S.Ressl, S.Hattar, A.T.Brunger, M.Missler, T.C.Sudhof (2016). Expression of C1ql3 in Discrete Neuronal Populations Controls Efferent Synapse Numbers and Diverse Behaviors. Neuron 91, 1034-1051 (2016).

 J.-P.Colletier, M.R.Sawaya, M.Gingery, J.A.Rodriguez, D.Cascio, A.S.Brewster, T.Michels-Clark, R.H.Hice, N.Coquelle, S.Boutet, G.J.Williams, M.Messerschmidt, D.P.DePonte, R.G.Sierra, H.Laksmono, J.E.Koglin, M.S.Hunter, H-W.Park, M.Uervirojnangkoorn, D.K.Bideshi, A.T.Brunger, B.A.Federici, N.K.Sauter, D.S.Eisenberg. De novo phasing with X-ray laser reveals mosquito larvicide BinAB structure. Nature 539 43-47 (2016).

 Y.Lai, U.B.Choi, Y.Zhang, M.Zhao, R.A.Pfuetzner, A.L.Wang, J.Diao, A.T.Brunger. N-terminal domain of complexin independently activates calcium-triggered fusion. Proc. Natl. Acad. Sci. USA 113, E4698-E4707 (2016).

 S.Malmersjo, S.D.Palma, J.Diao, Y.Lai, R.A.Pfuetzner, A.L.Wang, M.A.McMahon, A.Hayer, M.Porteus, B.Bodenmiller, A.T.Brunger, T.Meyer. Phosphorylation of residues inside the SNARE complex suppresses secretory vesicle fusion, EMBO J. 35, 1810-1821 (2016).

 U.B.Choi, M.Zhao, Y.Zhang, Y.Lai, A.T.Brunger. Complexin induces a conformational change at the membrane-proximal C-terminal end of the SNARE complex. Elife 5 e16886 (2016).

Key Publications (out of over 280)

 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).

 K.Weninger, M.E.Bowen, U.B.Choi, S.Chu, and A.T.Brunger, Accessory proteins stabilize the acceptor complex for synaptobrevin, the 1:1 syntaxin/SNAP-25 complex. Structure 16, 308-320 (2008).

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

 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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