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

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.

SUBMITTER: Chatterjee D 

PROVIDER: S-EPMC5882645 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature