Vesicle trafficking occurs between subcellular compartments in eukaryotic animal cells, which is responsible for cellular homeostasis. Coat proteins play a central role in the intracellular transport by coupling two major functions, bending membrane to generate transport carriers and binding to cargoes for their sorting into these carriers.

Well-characterized coat protein complexes include COPI, COPII and Clathrin, while sorting nexins (SNXs) have been found to act as coat proteins in endosomal pathways that include recycling from endosomes to the plasma membrane and retrieval from endosomes to the Golgi complex, such as endosomal recycling of cargoes, including the cation-independent mannose-6-phosphate receptor and semaphorin 4C.

In a study published in PNAS, SUN Fei's group from Institute of Biophysics of the Chinese Academy of Sciences, collaborating with Victor Hsu's group from Division of Rheumatology, Inflammation and Immunity of Brigham and Women's Hospital, and Department of Medicine of Harvard Medical School, revealed how SNX1 is organized on membrane to explain its ability and mechanism to deform membrane by cryo-electron microscopy (cryo-EM) helical reconstruction technique.

The researchers first resolved two helical assemble structures with different diameters but similar assembling mechanism.

These structures showed that there is one SNX1 dimer forming an asymmetric unit of the helical packing, oriented with its concave surface facing the membrane. Along the same helical row, two adjacent SNX1 dimers interact with each other through short lateral contacts formed by the BAR domain. The crosslinking of these parallel rows is mediated through the PX domain from one dimer in one helical row interacting with the BAR domain from another dimer residing in an adjacent helical row.

Besides, they found that the linker region between the BAR and PX domains of SNX1 plays an important role in membrane binding and tubulation, which is predicted to involve an amphipathic helix, and the PI3P binding site plays a significant role in mediating electrostatic interactions with the negatively charged membrane surface.

The researchers compared the SNX1 structure with a previously elucidated structure of an endosomal coat complex formed by retromer coupled to Vps5 (yeast homolog of SNX1), and revealed that Vps5 exists in a more compact state when assembled into the retromer-SNX coat complex.

This study advances the molecular understanding of how a SNX deforms membrane. The comparison provides insight into intermediary stages of assembly that results in the formation of the retromer-SNX coat complex on membrane.