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+

6MTI の概要

• エントリーDOI: 10.2210/pdb6mti/pdb
• EMDBエントリー: 9231
• 分子名称: Synaptotagmin-1, Vesicle-associated membrane protein 2, Syntaxin-1A, ... (7 entities in total)
• 機能のキーワード: snare, lipid nanotubes, exocytosis
• 由来する生物種: Rattus norvegicus (Rat); 詳細
• タンパク質・核酸の鎖数: 30
• 化学式量合計: 347964.38

構造登録者

Grushin, K.,Wang, J.,Coleman, J.,Rothman, J.,Sindelar, C.,Krishnakumar, S. (登録日: 2018-10-19, 公開日: 2019-04-24, 最終更新日: 2024-03-13)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (10.4 Å)