Structural Basis of the Migfilin-Filamin Interaction and Competition with Integrin β Tails

• DOI: 10.1074/jbc.m802592200
• Publication Date: 2008-10-02T00:13:31Z
• Authors: Yatish Lad; Pengju Jiang; Salla Ruskamo; David S. Harburger; Jari Ylänne; Iain D. Campbell; David A. Calderwood
• Keywords: FLNA

A link between sites of cell adhesion and the cytoskeleton is essential for regulation shape, motility, signaling. Migfilin a recently identified adaptor protein that localizes at cell-cell cell-extracellular matrix sites, where it thought to provide by interacting with actin cross-linking filamin. Here we have used x-ray crystallography, NMR spectroscopy, protein-protein interaction studies investigate molecular basis migfilin binding We report N-terminal portion can bind all three human filamins (FLNa, -b, or -c) there are multiple migfilin-binding in FLNa. Human composed an actin-binding domain followed 24 immunoglobulin-like (IgFLN) domains find binds preferentially IgFLNa21 more weakly IgFLNa19 -22. The filamin-binding site localized Pro(5) Pro(19) CD face beta-sandwich. This similar previously characterized beta 7 integrin-IgFLNa21 integrin tails compete one another IgFLNa21. suggests competition filamin ligands common on IgFLN may general means modulating interactions In this specific case, displacement from mechanism switching different integrin-cytoskeleton linkages.