Architecture of the synaptotagmin–SNARE machinery for neuronal exocytosis

Qiangjun Zhou, Ying Lai, Taulant Bacaj, Minglei Zhao, Artem Y. Lyubimov, Monarin Uervirojnangkoorn, Oliver B. Zeldin, Aaron S. Brewster, Nicholas K. Sauter, Aina E. Cohen, S. Michael Soltis, Roberto Alonso-Mori, Matthieu Chollet, Henrik T. Lemke, Richard A. Pfuetzner, Ucheor B. Choi, William I. Weis, Jiajie Diao, Thomas C. Südhof () and Axel T. Brunger ()
Additional contact information
Qiangjun Zhou: Howard Hughes Medical Institute, Stanford University
Ying Lai: Howard Hughes Medical Institute, Stanford University
Taulant Bacaj: Howard Hughes Medical Institute, Stanford University
Minglei Zhao: Howard Hughes Medical Institute, Stanford University
Artem Y. Lyubimov: Howard Hughes Medical Institute, Stanford University
Monarin Uervirojnangkoorn: Howard Hughes Medical Institute, Stanford University
Oliver B. Zeldin: Howard Hughes Medical Institute, Stanford University
Aaron S. Brewster: Lawrence Berkeley National Laboratory
Nicholas K. Sauter: Lawrence Berkeley National Laboratory
Aina E. Cohen: SLAC National Accelerator Laboratory
S. Michael Soltis: SLAC National Accelerator Laboratory
Roberto Alonso-Mori: SLAC National Accelerator Laboratory
Matthieu Chollet: SLAC National Accelerator Laboratory
Henrik T. Lemke: SLAC National Accelerator Laboratory
Richard A. Pfuetzner: Howard Hughes Medical Institute, Stanford University
Ucheor B. Choi: Howard Hughes Medical Institute, Stanford University
William I. Weis: Molecular and Cellular Physiology, and Photon Science, Stanford University
Jiajie Diao: Howard Hughes Medical Institute, Stanford University
Thomas C. Südhof: Howard Hughes Medical Institute, Stanford University
Axel T. Brunger: Howard Hughes Medical Institute, Stanford University

Nature, 2015, vol. 525, issue 7567, 62-67

Abstract: Abstract Synaptotagmin-1 and neuronal SNARE proteins have central roles in evoked synchronous neurotransmitter release; however, it is unknown how they cooperate to trigger synaptic vesicle fusion. Here we report atomic-resolution crystal structures of Ca2+- and Mg2+-bound complexes between synaptotagmin-1 and the neuronal SNARE complex, one of which was determined with diffraction data from an X-ray free-electron laser, leading to an atomic-resolution structure with accurate rotamer assignments for many side chains. The structures reveal several interfaces, including a large, specific, Ca2+-independent and conserved interface. Tests of this interface by mutagenesis suggest that it is essential for Ca2+-triggered neurotransmitter release in mouse hippocampal neuronal synapses and for Ca2+-triggered vesicle fusion in a reconstituted system. We propose that this interface forms before Ca2+ triggering, moves en bloc as Ca2+ influx promotes the interactions between synaptotagmin-1 and the plasma membrane, and consequently remodels the membrane to promote fusion, possibly in conjunction with other interfaces.

Date: 2015
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/nature14975 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:525:y:2015:i:7567:d:10.1038_nature14975

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature14975

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().