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首页> 外文期刊>Nature >Structure of the membrane-assembled retromer coat determined by cryo- electron tomography
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Structure of the membrane-assembled retromer coat determined by cryo- electron tomography

机译：薄膜组装的后涂层的结构通过冷冻电子断层扫描确定

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Eukaryotic cells traffic proteins and lipids between different compartments using protein-coated vesicles and tubules. The retromer complex is required to generate cargo-selective tubulovesicular carriers from endosomal membranes(1-3). Conserved in eukaryotes, retromer controls the cellular localization and homeostasis of hundreds of transmembrane proteins, and its disruption is associated with major neurodegenerative disorders(4-7). How retromer is assembled and how it is recruited to form coated tubules is not known. Here we describe the structure of the retromer complex (Vps26-Vps29-Vps35) assembled on membrane tubules with the bin/amphiphysin/rvs-domain-containing sorting nexin protein Vps5, using cryo-electron tomography and subtomogram averaging. This reveals a membrane-associated Vps5 array, from which arches of retromer extend away from the membrane surface. Vps35 forms the ` legs' of these arches, and Vps29 resides at the apex where it is free to interact with regulatory factors. The bases of the arches connect to each other and to Vps5 through Vps26, and the presence of the same arches on coated tubules within cells confirms their functional importance. Vps5 binds to Vps26 at a position analogous to the previously described cargo-and Snx3-binding site, which suggests the existence of distinct retromer-sorting nexin assemblies. The structure provides insight into the architecture of the coat and its mechanism of assembly, and suggests that retromer promotes tubule formation by directing the distribution of sorting nexin proteins on the membrane surface while providing a scaffold for regulatory-protein interactions.
机译：真核细胞使用蛋白包被的囊泡和小管在不同的区室之间运输蛋白和脂质。需要逆转录复合物才能从内体膜生成货物选择性微管网状载体（1-3）。真核生物中保守的保守分子控制着数百个跨膜蛋白的细胞定位和稳态，其破坏与主要的神经退行性疾病有关（4-7）。还不知道逆转录酶如何组装以及如何募集以形成包被的小管。在这里，我们使用冷冻电子断层扫描和断层平均法，描述了在具有小管/两性/ rvs结构域分类神经蛋白Vps5的膜小管上组装的逆转录复合物（Vps26-Vps29-Vps35）的结构。这揭示了膜相关的Vps5阵列，后倾拱从该阵列延伸离开膜表面。 Vps35构成了这些弓的“腿”，而Vps29位于顶点，可以自由与调节因子相互作用。弓形的基部相互连接，并通过Vps26连接到Vps5，并且细胞内带涂层的细管上存在相同的弓形，证实了它们的功能重要性。 Vps5在类似于先前描述的货物和Snx3结合位点的位置上与Vps26结合，这表明存在不同的逆向体分选神经素装配体。该结构提供了对外套结构及其组装机​​理的深入了解，并表明，翻新异构体通过指导分类的nexin蛋白在膜表面的分布来促进肾小管的形成，同时为调节蛋白相互作用提供了一个支架。

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