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

 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, 10.1073/pnas.1708492114 (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).

 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).

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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