8E22

VPS37A_21-148

8E22 の概要

• エントリーDOI: 10.2210/pdb8e22/pdb
• NMR情報: BMRB: 31039
• 分子名称: Vacuolar protein sorting-associated protein 37A (1 entity in total)
• 機能のキーワード: escrt, autophagy, structural protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 14571.69

構造登録者

Tian, F.,Ye, Y.S. (登録日: 2022-08-12, 公開日: 2023-08-09, 最終更新日: 2024-05-01)

主引用文献

Ye, Y.,Liang, X.,Wang, G.,Bewley, M.C.,Hamamoto, K.,Liu, X.,Flanagan, J.M.,Wang, H.G.,Takahashi, Y.,Tian, F.
Identification of membrane curvature sensing motifs essential for VPS37A phagophore recruitment and autophagosome closure.
Commun Biol, 7:334-334, 2024

PubMed Abstract: VPS37A, an ESCRT-I complex component, is required for recruiting a subset of ESCRT proteins to the phagophore for autophagosome closure. However, the mechanism by which VPS37A is targeted to the phagophore remains obscure. Here, we demonstrate that the VPS37A N-terminal domain exhibits selective interactions with highly curved membranes, mediated by two membrane-interacting motifs within the disordered regions surrounding its Ubiquitin E2 variant-like (UEVL) domain. Site-directed mutations of residues in these motifs disrupt ESCRT-I localization to the phagophore and result in defective phagophore closure and compromised autophagic flux in vivo, highlighting their essential role during autophagy. In conjunction with the UEVL domain, we postulate that these motifs guide a functional assembly of the ESCRT machinery at the highly curved tip of the phagophore for autophagosome closure. These results advance the notion that the distinctive membrane architecture of the cup-shaped phagophore spatially regulates autophagosome biogenesis.

PubMed: 38491121
DOI: 10.1038/s42003-024-06026-7

実験手法

SOLUTION NMR