6n5z | pdb_00006n5z
Crystal structure of the SNX5 PX domain in complex with the Sema4C
Structural highlights
Function[SNX5_HUMAN] May be involved in several stages of intracellular trafficking. Plays a role in macropinocytosis. Plays a role in the internalization of EGFR after EGF stimulation.[1] [2] Publication Abstract from PubMedProtein trafficking requires coat complexes that couple recognition of sorting motifs in transmembrane cargoes with biogenesis of transport carriers. The mechanisms of cargo transport through the endosomal network are poorly understood. Here, we identify a sorting motif for endosomal recycling of cargoes, including the cation-independent mannose-6-phosphate receptor and semaphorin 4C, by the membrane tubulating BAR domain-containing sorting nexins SNX5 and SNX6. Crystal structures establish that this motif folds into a beta-hairpin, which binds a site in the SNX5/SNX6 phox homology domains. Over sixty cargoes share this motif and require SNX5/SNX6 for their recycling. These include cargoes involved in neuronal migration and a Drosophila snx6 mutant displays defects in axonal guidance. These studies identify a sorting motif and provide molecular insight into an evolutionary conserved coat complex, the 'Endosomal SNX-BAR sorting complex for promoting exit 1' (ESCPE-1), which couples sorting motif recognition to the BAR-domain-mediated biogenesis of cargo-enriched tubulo-vesicular transport carriers. Molecular identification of a BAR domain-containing coat complex for endosomal recycling of transmembrane proteins.,Simonetti B, Paul B, Chaudhari K, Weeratunga S, Steinberg F, Gorla M, Heesom KJ, Bashaw GJ, Collins BM, Cullen PJ Nat Cell Biol. 2019 Oct;21(10):1219-1233. doi: 10.1038/s41556-019-0393-3. Epub, 2019 Oct 1. PMID:31576058[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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