2N31

Tom1 negatively modulates binding of Tollip to phosphatidylinositol 3-phosphate via a coupled folding and binding mechanism

Summary for 2N31

• Entry DOI: 10.2210/pdb2n31/pdb
• NMR Information: BMRB: 25632
• Descriptor: Toll interacting protein variant (1 entity in total)
• Functional Keywords: immune system
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 6131.82

Authors

Xiao, S.,Armstrong, G.,Capelluto, D. (deposition date: 2015-05-19, release date: 2015-09-16, Last modification date: 2024-05-15)

Primary citation

Xiao, S.,Brannon, M.K.,Zhao, X.,Fread, K.I.,Ellena, J.F.,Bushweller, J.H.,Finkielstein, C.V.,Armstrong, G.S.,Capelluto, D.G.
Tom1 Modulates Binding of Tollip to Phosphatidylinositol 3-Phosphate via a Coupled Folding and Binding Mechanism.
Structure, 23:1910-1920, 2015

PubMed Abstract: Early 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.

PubMed: 26320582
DOI: 10.1016/j.str.2015.07.017

Experimental method

SOLUTION NMR