6MTI

Synaptotagmin-1 C2A, C2B domains and SNARE-pin proteins (5CCI) individually docked into Cryo-EM map of C2AB-SNARE complexes helically organized on lipid nanotube surface in presence of Mg2+

Summary for 6MTI

• Entry DOI: 10.2210/pdb6mti/pdb
• EMDB information: 9231
• Descriptor: Synaptotagmin-1, Vesicle-associated membrane protein 2, Syntaxin-1A, ... (7 entities in total)
• Functional Keywords: snare, lipid nanotubes, exocytosis
• Biological source: Rattus norvegicus (Rat); More
• Total number of polymer chains: 30
• Total formula weight: 347964.38

Authors

Grushin, K.,Wang, J.,Coleman, J.,Rothman, J.,Sindelar, C.,Krishnakumar, S. (deposition date: 2018-10-19, release date: 2019-04-24, Last modification date: 2024-03-13)

Primary citation

Grushin, K.,Wang, J.,Coleman, J.,Rothman, J.E.,Sindelar, C.V.,Krishnakumar, S.S.
Structural basis for the clamping and Ca2+activation of SNARE-mediated fusion by synaptotagmin.
Nat Commun, 10:2413-2413, 2019

PubMed Abstract: Synapotagmin-1 (Syt1) interacts with both SNARE proteins and lipid membranes to synchronize neurotransmitter release to calcium (Ca) influx. Here we report the cryo-electron microscopy structure of the Syt1-SNARE complex on anionic-lipid containing membranes. Under resting conditions, the Syt1 C2 domains bind the membrane with a magnesium (Mg)-mediated partial insertion of the aliphatic loops, alongside weak interactions with the anionic lipid headgroups. The C2B domain concurrently interacts the SNARE bundle via the 'primary' interface and is positioned between the SNAREpins and the membrane. In this configuration, Syt1 is projected to sterically delay the complete assembly of the associated SNAREpins and thus, contribute to clamping fusion. This Syt1-SNARE organization is disrupted upon Ca-influx as Syt1 reorients into the membrane, likely displacing the attached SNAREpins and reversing the fusion clamp. We thus conclude that the cation (Mg/Ca) dependent membrane interaction is a key determinant of the dual clamp/activator function of Synaptotagmin-1.

PubMed: 31160571
DOI: 10.1038/s41467-019-10391-x

Experimental method

ELECTRON MICROSCOPY (10.4 Å)