2n31
From Proteopedia
Tom1 negatively modulates binding of Tollip to phosphatidylinositol 3-phosphate via a coupled folding and binding mechanism
Structural highlights
FunctionTOLIP_HUMAN Component of the signaling pathway of IL-1 and Toll-like receptors. Inhibits cell activation by microbial products. Recruits IRAK1 to the IL-1 receptor complex. Inhibits IRAK1 phosphorylation and kinase activity.[1] Publication Abstract from PubMedEarly endosomes represent the first sorting station for vesicular ubiquitylated cargo. Tollip, through its C2 domain, associates with endosomal phosphatidylinositol 3-phosphate (PtdIns(3)P) and binds ubiquitylated cargo in these compartments via its C2 and CUE domains. Tom1, through its GAT domain, is recruited to endosomes by binding to the Tollip Tom1-binding domain (TBD) through an unknown mechanism. Nuclear magnetic resonance data revealed that Tollip TBD is a natively unfolded domain that partially folds at its N terminus when bound to Tom1 GAT through high-affinity hydrophobic contacts. Furthermore, this association abrogates binding of Tollip to PtdIns(3)P by additionally targeting its C2 domain. Tom1 GAT is also able to bind ubiquitin and PtdIns(3)P at overlapping sites, albeit with modest affinity. We propose that association with Tom1 favors the release of Tollip from endosomal membranes, allowing Tollip to commit to cargo trafficking. Tom1 Modulates Binding of Tollip to Phosphatidylinositol 3-Phosphate via a Coupled Folding and Binding Mechanism.,Xiao S, Brannon MK, Zhao X, Fread KI, Ellena JF, Bushweller JH, Finkielstein CV, Armstrong GS, Capelluto DG Structure. 2015 Oct 6;23(10):1910-20. doi: 10.1016/j.str.2015.07.017. Epub 2015, Aug 27. PMID:26320582[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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