2mxc
From Proteopedia
Solution structure of the full length sorting nexin 3
Structural highlights
DiseaseSNX3_HUMAN MMEP syndrome. The gene represented in this entry may be involved in disease pathogenesis. A chromosomal aberration involving SNX3 has been found in patients with syndromic microphthalmia. Translocation t(6;13)(q21;q12). FunctionSNX3_HUMAN Phosphoinositide-binding protein required for multivesicular body formation. Specifically binds phosphatidylinositol 3-phosphate (PtdIns(P3)). Plays a role in protein transport between cellular compartments. Promotes stability and cell surface expression of epithelial sodium channel (ENAC) subunits SCNN1A and SCNN1G (By similarity). Not involved in EGFR degradation.[1] [2] Publication Abstract from PubMedSorting nexins anchor trafficking machines to membranes by binding phospholipids. The paradigm of the superfamily is sorting nexin 3 (SNX3), which localizes to early endosomes by recognizing phosphatidylinositol 3-phosphate (PI3P) to initiate retromer-mediated segregation of cargoes to the trans-Golgi network (TGN). Here we report the solution structure of full length human SNX3, and show that PI3P recognition is accompanied by bilayer insertion of a proximal loop in its extended Phox homology (PX) domain. Phosphoinositide (PIP) binding is completely blocked by cancer-linked phosphorylation of a conserved serine beside the stereospecific PI3P pocket. This "PIP-stop" releases endosomal SNX3 to the cytosol, and reveals how protein kinases control membrane assemblies. It constitutes a widespread regulatory element found across the PX superfamily and throughout evolution including of fungi and plants. This illuminates the mechanism of a biological switch whereby structured PIP sites are phosphorylated to liberate protein machines from organelle surfaces. Phosphorylation of conserved phosphoinositide binding pocket regulates sorting nexin membrane targeting.,Lenoir M, Ustunel C, Rajesh S, Kaur J, Moreau D, Gruenberg J, Overduin M Nat Commun. 2018 Mar 8;9(1):993. doi: 10.1038/s41467-018-03370-1. PMID:29520003[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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