複合体: Mouse retromer (VPS26/VPS35/VPS29) tetramer of heterotrimers
タンパク質・ペプチド: Vacuolar protein sorting-associated protein 29
タンパク質・ペプチド: Vacuolar protein sorting-associated protein 35
キーワード
retromer / membrane trafficking / endosomal trafficking / membrane coat complexes / PROTEIN TRANSPORT
機能・相同性
機能・相同性情報
WNT ligand biogenesis and trafficking / neurotransmitter receptor transport, endosome to plasma membrane / negative regulation of protein localization / mitochondrion-derived vesicle / negative regulation of protein homooligomerization / tubular endosome / regulation of terminal button organization / regulation of dendritic spine maintenance / positive regulation of Wnt protein secretion / retromer, cargo-selective complex ...WNT ligand biogenesis and trafficking / neurotransmitter receptor transport, endosome to plasma membrane / negative regulation of protein localization / mitochondrion-derived vesicle / negative regulation of protein homooligomerization / tubular endosome / regulation of terminal button organization / regulation of dendritic spine maintenance / positive regulation of Wnt protein secretion / retromer, cargo-selective complex / vacuolar protein processing / mitochondrion to lysosome vesicle-mediated transport / negative regulation of lysosomal protein catabolic process / positive regulation of locomotion involved in locomotory behavior / negative regulation of late endosome to lysosome transport / positive regulation of dopamine receptor signaling pathway / Golgi to vacuole transport / neurotransmitter receptor transport, endosome to postsynaptic membrane / positive regulation of dopamine biosynthetic process / protein localization to endosome / voluntary musculoskeletal movement / retromer complex / mitochondrial fragmentation involved in apoptotic process / transcytosis / regulation of protein metabolic process / dopaminergic synapse / regulation of synapse maturation / endocytic recycling / regulation of mitochondrion organization / retrograde transport, endosome to Golgi / positive regulation of protein localization to cell periphery / positive regulation of mitochondrial fission / lysosome organization / regulation of postsynapse assembly / D1 dopamine receptor binding / regulation of protein stability / intracellular protein transport / negative regulation of inflammatory response / protein destabilization / modulation of chemical synaptic transmission / positive regulation of protein catabolic process / late endosome / positive regulation of canonical Wnt signaling pathway / presynapse / early endosome / lysosome / endosome membrane / endosome / neuron projection / postsynaptic density / postsynapse / negative regulation of gene expression / neuronal cell body / positive regulation of gene expression / synapse / perinuclear region of cytoplasm / glutamatergic synapse / mitochondrion / membrane / metal ion binding / cytoplasm / cytosol 類似検索 - 分子機能
Vacuolar protein sorting-associated protein 35 / Vacuolar protein sorting-associated protein 35, C-terminal / Vacuolar protein sorting-associated protein 35 / Vacuolar protein sorting-associated protein 29 / Phosphodiesterase MJ0936/Vps29 / Calcineurin-like phosphoesterase domain, lpxH-type / Calcineurin-like phosphoesterase superfamily domain / Metallo-dependent phosphatase-like / Armadillo-type fold 類似検索 - ドメイン・相同性
Vacuolar protein sorting-associated protein 35 / Vacuolar protein sorting-associated protein 29 類似検索 - 構成要素
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
引用
ジャーナル: Structure / 年: 2020 タイトル: Mammalian Retromer Is an Adaptable Scaffold for Cargo Sorting from Endosomes. 著者: Amy K Kendall / Boyang Xie / Peng Xu / Jue Wang / Rodger Burcham / Meredith N Frazier / Elad Binshtein / Hui Wei / Todd R Graham / Terunaga Nakagawa / Lauren P Jackson / 要旨: 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 ...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.