2mxc

Solution structure of the full length sorting nexin 3

spinqualitylabelsall models 2mxc Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2mxc is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Solution NMR Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease SNX3_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). Function SNX3_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. Publication Abstract from PubMed Sorting 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Sorting nexin 3D structures

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