4gxb | pdb_00004gxb
Structure of the SNX17 atypical FERM domain bound to the NPxY motif of P-selectin
Structural highlights
Function[SNX17_HUMAN] Critical regulator of endosomal recycling of numerous receptors, channels, and other transmembrane proteins. Binds to NPxY sequences in the cytoplasmic tails of target cargos. Plays a role in the sorting of endocytosed LRP1 and APP, and prevents their degradation. Required for maintenance of normal cell surface levels of APP and LRP1. Recycles internalized integrins ITGB1, ITGB5 and their associated alpha subunits, preventing them from lysosomal degradation. Interacts with membranes containing phosphatidylinositol 3-phosphate (PtdIns(3P)).[1] [2] [3] [4] [5] [6] [LYAM3_MOUSE] Ca(2+)-dependent receptor for myeloid cells that binds to carbohydrates on neutrophils and monocytes. Mediates the interaction of activated endothelial cells or platelets with leukocytes. The ligand recognized is sialyl-Lewis X. Mediates rapid rolling of leukocyte rolling over vascular surfaces during the initial steps in inflammation through interaction with PSGL1.[7] Publication Abstract from PubMedTransit of proteins through the endosomal organelle following endocytosis is critical for regulating the homeostasis of cell-surface proteins and controlling signal transduction pathways. However, the mechanisms that control these membrane-transport processes are poorly understood. The Phox-homology (PX) domain-containing proteins sorting nexin (SNX) 17, SNX27, and SNX31 have emerged recently as key regulators of endosomal recycling and bind conserved Asn-Pro-Xaa-Tyr-sorting signals in transmembrane cargos via an atypical band, 4.1/ezrin/radixin/moesin (FERM) domain. Here we present the crystal structure of the SNX17 FERM domain bound to the sorting motif of the P-selectin adhesion protein, revealing both the architecture of the atypical FERM domain and the molecular basis for recognition of these essential sorting sequences. We further show that the PX-FERM proteins share a promiscuous ability to bind a wide array of putative cargo molecules, including receptor tyrosine kinases, and propose a model for their coordinated molecular interactions with membrane, cargo, and regulatory proteins. Structural basis for endosomal trafficking of diverse transmembrane cargos by PX-FERM proteins.,Ghai R, Bugarcic A, Liu H, Norwood SJ, Skeldal S, Coulson EJ, Li SS, Teasdale RD, Collins BM Proc Natl Acad Sci U S A. 2013 Feb 19;110(8):E643-52. doi:, 10.1073/pnas.1216229110. Epub 2013 Feb 4. PMID:23382219[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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