作者
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
发表日期
2020/4/7
期刊
Structure
卷号
28
期号
4
页码范围
393-405. e4
出版商
Elsevier
简介
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 …
引用总数
20202021202220232024612846
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