Structural insights into membrane remodeling by SNX1

Significance Coat proteins play a central role in the intracellular transport pathways by coupling two main functions: bending the membrane to generate transport carriers and binding to cargoes for their sorting into these carriers. Studies thus far have mostly solved the structure of coat proteins in solution, but their functional form requires assembly on the membrane into protein complexes. Here, we have pursued cryo-EM to reveal in molecular detail how SNX1 assembles on the membrane to deform the membrane. When compared to a previously solved retromer-SNX complex, our elucidation also suggests how retromer affects SNX in this complex as well as the intermediary stages of this coat assembly. 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.

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