National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China;
Proc Natl Acad Sci U S A. 2021 Mar 9;118(10). doi: 10.1073/pnas.2022614118.
The sorting nexin (SNX) family of proteins deform the membrane to generate transport carriers in endosomal pathways. Here, we elucidate how a prototypic member, SNX1, acts in this process. Performing cryoelectron microscopy, we find that SNX1 assembles into a protein lattice that consists of helical rows of SNX1 dimers wrapped around tubular membranes in a crosslinked fashion. We also visualize the details of this structure, which provides a molecular understanding of how various parts of SNX1 contribute to its ability to deform the membrane. Moreover, we have compared the SNX1 structure with a previously elucidated structure of an endosomal coat complex formed by retromer coupled to a SNX, which reveals how the molecular organization of the SNX in this coat complex is affected by retromer. The comparison also suggests insight into intermediary stages of assembly that results in the formation of the retromer-SNX coat complex on the membrane.
分选连接蛋白(SNX)家族的蛋白可使细胞膜变形,在胞内体途径中生成运输载体。在此,我们阐明了典型成员 SNX1 在这个过程中的作用。通过冷冻电镜,我们发现 SNX1 组装成一个蛋白晶格,该晶格由 SNX1 二聚体的螺旋排组成,以交联的方式缠绕在管状膜上。我们还观察到了这个结构的细节,这为理解 SNX1 的各个部分如何有助于其膜变形能力提供了分子基础。此外,我们比较了 SNX1 结构与先前阐明的由 retromer 与 SNX 形成的内体包被复合物的结构,揭示了 retromer 如何影响包被复合物中 SNX 的分子组织。这种比较还为形成膜上 retromer-SNX 包被复合物的组装中间阶段提供了一些见解。