Research Highlights
Our laboratory studies the molecular mechanisms of neurotransmitter release, and how these mechanisms relate to physiological function.
Synaptic V-ATPase-synaptophysin complex
Inhibition of calcium-triggered fusion
Calcium triggering: SNARE/complexin/synaptotagmin complex
Disassembly of the SNARE complex by NSF/SNAP
Selected Publications
R.G.Held, J.Liang, A.T.Brunger. Nanoscale architecture of synaptic vesicles and scaffolding complexes revealed by cryo-electron tomography. Proc.Natl. Acad. Sci. USA, https://doi.org/10.1073/pnas.2403136121 (2024).
C.Wang, W.Jiang, J.Leitz, K.Yang, L.Esquivies, X.Wang, X.Shen, R.Held, D.J.Adams, T.Basta, L. Hampton, R.Jian, L.Jiang, M.H.B.Stowell, W.Baumeister, Q.Guo, A.T.Brunger. Structure and topography of the synaptic V-ATPase–synaptophysin complex. Nature 631, 899-904, https://doi.org/10.1038/s41586-024-07610-x (2024).
J.Leitz, C.Wang, L.Esquivies, R.A.Pfuetzner, J.J.Peters, S.Couoh-Cardel, A.Wang, A.T.Brunger. Beyond the MUN domain, Munc13 controls priming and depriming of synaptic vesicles. Cell Reports, https://doi.org/10.1016/j.celrep.2024.114026 (2024).
K.Yang, C.Wang, A.J.B.Kreutzberger, K.I.White, R.A.Pfuetzner, L.Esquivies, T.Kirchhausen, A.T.Brunger. Structure-based design of a SARS-CoV-2 Omicron-specific inhibitor. Proc.Natl.Acad.Sci.USA 120, doi:10.1073/pnas.2300360120 (2023).
K.Yang, C.Wang, A.J.B.Kreutzberger, R. Ojha, S.Kuivanen, S.Couoh-Cardel, S.Muratcioglu, T.J.Eisen, K.I.White, R.G.Held, S.Subramanian, M.Kendra, R.A.Pfuetzner, L.Esquivies, C.Doyle, J.Kuriyan, O.Vapalahti, G.Balistreri, T.Kirchhausen,A.T.Brunger. Nanomolar inhibition of SARS-CoV-2 infection by an unmodified peptide targeting the prehairpin intermediate of the spike protein. Proc.Natl.Acad.Sci. USA 119, e2210990119. (2022).
Y.Lai, G.Fois, J.R.Flores, M.J.Tuvim, Q.Zhou, K.Yang, J.Leitz, J.Peters, Y.Zhang, R.A.Pfuetzner, L.Esquivies, P.Jones, M.Frick, B.F.Dickey, A.T.Brunger. Inhibition of Ca2+-triggered secretion by hydrocarbon-stapled peptides. Nature 603, 949–956 (2022).
J.J.Peters, J.Leitz, Q.Guo, F.Beck, W.Baumeister, A.T.Brunger. A feature-guided, focused 3D signal permutation method for subtomogram averaging. J. Struct. Biol. 214, 107851 doi:10.1016/j.jsb.2022.107851 (2022).
K.Yang, C.Wang, K.I.White, R.A.Pfuetzner, L.Esquivies, A.T.Brunger. Structural conservation among variants of the SARS-CoV-2 spike postfusion bundle. Proc.Natl.Acad.Sci. USA 119, e2119467119. doi:https://doi.org/10.1073/pnas.2119467119 (2022).
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 7, e38888. 10.7554/eLife.38888 (2018).
U.B. Choi, M. Zhao, K.I. White, R.A. Pfuetzner, L. Esquivies, Q. Zhou, A.T. Brunger (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, Y. 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).
