NMR structure, dynamics and interactions of the integrin β2 cytoplasmic tail with filamin domain IgFLNa21

• Main Authors: Chatterjee, Deepak, Tan, Suet-Mien, Bhattacharjya, Surajit, Lu, Lewis Zhiping
• Other Authors: School of Biological Sciences
• Format: Article
• Language: English
• Published: 2018
• Subjects: Integrin; Nuclear Magnetic Resonance (NMR)
• Online Access: https://hdl.handle.net/10356/87392; http://hdl.handle.net/10220/45389
• Institution: Nanyang Technological University

Integrins are transmembrane proteins that mediate cell adhesion and migration. Each integrin is a heterodimer formed by an α and a β 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 β2 CT that contains a TTT-motif. Based on x-ray crystallography, it has been reported that the integrin β2 CT forms a β strand that docks into the β strands C and D of IgFLNa21. In this study, we performed solution NMR analyses of IgFLNa21 in the presence of integrin β2 CT peptides, and hybrid IgFLNa21, a construct of covalently linked IgFLNa21 and β2 CT. The atomic resolution structure of the hybrid IgFLNa21 demonstrated conserved binding mode with β2 CT. Although, 15N relaxation, model free analyses and H-D exchange studies have uncovered important insights into the conformational dynamics and stability of β2 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 β2 CT.