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Default NMR Structure, Dynamics and Interactions of the Integrin ?2 Cytoplasmic Tail with Filamin Domain IgFLNa21.

NMR Structure, Dynamics and Interactions of the Integrin ?2 Cytoplasmic Tail with Filamin Domain IgFLNa21.

Related Articles NMR Structure, Dynamics and Interactions of the Integrin ?2 Cytoplasmic Tail with Filamin Domain IgFLNa21.

Sci Rep. 2018 Apr 03;8(1):5490

Authors: Chatterjee D, Zhiping LL, Tan SM, Bhattacharjya S

Abstract
Integrins are transmembrane proteins that mediate cell adhesion and migration. Each integrin is a heterodimer formed by an ? and a ? subunit. A large number of cytoplasmic proteins interact with the cytoplasmic tails (CTs) of integrins. The actin-binding cytoskeletal protein filamin A is a negative regulator of integrin activation. The IgFLNa21 domain of filamin A binds to the C-terminus of ?2 CT that contains a TTT-motif. Based on x-ray crystallography, it has been reported that the integrin ?2 CT forms a ? strand that docks into the ? strands C and D of IgFLNa21. In this study, we performed solution NMR analyses of IgFLNa21 in the presence of integrin ?2 CT peptides, and hybrid IgFLNa21, a construct of covalently linked IgFLNa21 and ?2 CT. The atomic resolution structure of the hybrid IgFLNa21 demonstrated conserved binding mode with ?2 CT. Although, 15N relaxation, model free analyses and H-D exchange studies have uncovered important insights into the conformational dynamics and stability of ?2 CT in complex with IgFLNa21. Such dynamical characteristics are likely to be necessary for the TTT-motif to serve as a phosphorylation switch that regulates filamin A binding to integrin ?2 CT.


PMID: 29615775 [PubMed - in process]



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