6VAB

Mouse retromer sub-structure: VPS35/VPS35 flat dimer

6VAB の概要

• エントリーDOI: 10.2210/pdb6vab/pdb
• EMDBエントリー: 21135
• 分子名称: Vacuolar protein sorting-associated protein 29, Vacuolar protein sorting-associated protein 35 (2 entities in total)
• 機能のキーワード: retromer, membrane trafficking, endosomal trafficking, membrane coat complexes, protein transport
• 由来する生物種: Mus musculus (Mouse); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 224686.79

構造登録者

Kendall, A.K.,Jackson, L.P. (登録日: 2019-12-17, 公開日: 2020-02-19, 最終更新日: 2024-03-06)

主引用文献

Kendall, A.K.,Xie, B.,Xu, P.,Wang, J.,Burcham, R.,Frazier, M.N.,Binshtein, E.,Wei, H.,Graham, T.R.,Nakagawa, T.,Jackson, L.P.
Mammalian Retromer Is an Adaptable Scaffold for Cargo Sorting from Endosomes.
Structure, 28:393-405.e4, 2020

PubMed Abstract: Metazoan retromer (VPS26/VPS35/VPS29) associates with sorting nexins on endosomal tubules to sort proteins to the trans-Golgi network or plasma membrane. Mechanisms of metazoan retromer assembly remain undefined. We combine single-particle cryoelectron microscopy with biophysical methods to uncover multiple oligomer structures. 2D class averages reveal mammalian heterotrimers; dimers of trimers; tetramers of trimers; and flat chains. These species are further supported by biophysical solution studies. We provide reconstructions of all species, including key sub-structures (∼5 Å resolution). Local resolution variation suggests that heterotrimers and dimers adopt multiple conformations. Our structures identify a flexible, highly conserved electrostatic dimeric interface formed by VPS35 subunits. We generate structure-based mutants to disrupt this interface in vitro. Equivalent mutations in yeast demonstrate a mild cargo-sorting defect. Our data suggest the metazoan retromer is an adaptable and plastic scaffold that accommodates interactions with different sorting nexins to sort multiple cargoes from endosomes their final destinations.

PubMed: 32027819
DOI: 10.1016/j.str.2020.01.009

実験手法

ELECTRON MICROSCOPY (4.9 Å)