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Title | Mammalian Retromer Is an Adaptable Scaffold for Cargo Sorting from Endosomes. |
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Journal, issue, pages | Structure, Vol. 28, Issue 4, Page 393-405.e4, Year 2020 |
Publish date | Apr 7, 2020 |
Authors | 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 / |
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 ...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. |
External links | Structure / PubMed:32027819 / PubMed Central |
Methods | EM (single particle) |
Resolution | 4.9 - 25.5 Å |
Structure data | EMDB-21101: EMDB-21116: EMDB-21117: EMDB-21118: EMDB-21119: EMDB-21135, PDB-6vab: EMDB-21136, PDB-6vac: |
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Keywords | PROTEIN TRANSPORT / retromer / membrane trafficking / endosomal trafficking / membrane coat complexes |