9BRT

Intact V-ATPase State 1 and synaptophysin complex in mouse brain isolated synaptic vesicles

これはPDB形式変換不可エントリーです。

9BRT の概要

• エントリーDOI: 10.2210/pdb9brt/pdb
• EMDBエントリー: 44843
• 分子名称: V-type proton ATPase subunit E 1, V-type proton ATPase 21 kDa proteolipid subunit c'', V-type proton ATPase subunit d 1, ... (17 entities in total)
• 機能のキーワード: v-atpase, synaptic vesicle, membrane protein
• 由来する生物種: Mus musculus (house mouse); 詳細
• タンパク質・核酸の鎖数: 33
• 化学式量合計: 1081501.71

構造登録者

Wang, C.,Jiang, W.,Yang, K.,Wang, X.,Guo, Q.,Brunger, A.T. (登録日: 2024-05-11, 公開日: 2024-06-19, 最終更新日: 2024-08-07)

主引用文献

Wang, C.,Jiang, W.,Leitz, J.,Yang, K.,Esquivies, L.,Wang, X.,Shen, X.,Held, R.G.,Adams, D.J.,Basta, T.,Hampton, L.,Jian, R.,Jiang, L.,Stowell, M.H.B.,Baumeister, W.,Guo, Q.,Brunger, A.T.
Structure and topography of the synaptic V-ATPase-synaptophysin complex.
Nature, 631:899-904, 2024

PubMed Abstract: Synaptic vesicles are organelles with a precisely defined protein and lipid composition, yet the molecular mechanisms for the biogenesis of synaptic vesicles are mainly unknown. Here we discovered a well-defined interface between the synaptic vesicle V-ATPase and synaptophysin by in situ cryo-electron tomography and single-particle cryo-electron microscopy of functional synaptic vesicles isolated from mouse brains. The synaptic vesicle V-ATPase is an ATP-dependent proton pump that establishes the proton gradient across the synaptic vesicle, which in turn drives the uptake of neurotransmitters. Synaptophysin and its paralogues synaptoporin and synaptogyrin belong to a family of abundant synaptic vesicle proteins whose function is still unclear. We performed structural and functional studies of synaptophysin-knockout mice, confirming the identity of synaptophysin as an interaction partner with the V-ATPase. Although there is little change in the conformation of the V-ATPase upon interaction with synaptophysin, the presence of synaptophysin in synaptic vesicles profoundly affects the copy number of V-ATPases. This effect on the topography of synaptic vesicles suggests that synaptophysin assists in their biogenesis. In support of this model, we observed that synaptophysin-knockout mice exhibit severe seizure susceptibility, suggesting an imbalance of neurotransmitter release as a physiological consequence of the absence of synaptophysin.

PubMed: 38838737
DOI: 10.1038/s41586-024-07610-x

実験手法

ELECTRON MICROSCOPY (4.3 Å)