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|Title:||The molecular basis of filamin binding to integrins and competition with talin|
|Citation:||Molecular Cell, 2006; 21(3):337-347|
|Tiila Kiema, Yatish Lad, Pengju Jiang, Camilla L. Oxley, Massimiliano Baldassarre, Kate L. Wegener, Iain D. Campbell, Jari Ylänne and David A. Calderwood|
|Abstract:||The ability of adhesion receptors to transmit biochemical signals and mechanical force across cell membranes depends on interactions with the actin cytoskeleton. Filamins are large, actin-crosslinking proteins that connect multiple transmembrane and signaling proteins to the cytoskeleton. Here, we describe the high-resolution structure of an interface between filamin A and an integrin adhesion receptor. When bound, the integrin β cytoplasmic tail forms an extended β strand that interacts with β strands C and D of the filamin immunoglobulin-like domain (IgFLN) 21. This interface is common to many integrins, and we suggest it is a prototype for other IgFLN domain interactions. Notably, the structurally defined filamin binding site overlaps with that of the integrin-regulator talin, and these proteins compete for binding to integrin tails, allowing integrin-filamin interactions to impact talin-dependent integrin activation. Phosphothreonine-mimicking mutations inhibit filamin, but not talin, binding, indicating that kinases may modulate this competition and provide additional means to control integrin functions.|
|Keywords:||NIH 3T3 Cells; Animals; Mice; Microfilament Proteins; Calpain; Contractile Proteins; Talin; Integrin beta Chains; Recombinant Fusion Proteins; Crystallography, X-Ray; Nuclear Magnetic Resonance, Biomolecular; Reproducibility of Results; Binding Sites; Amino Acid Sequence; Protein Conformation; Protein Structure, Tertiary; Protein Binding; Sequence Homology, Amino Acid; Models, Molecular; Molecular Sequence Data; Filamins|
|Rights:||Copyright 2006 Elsevier Inc.|
|Appears in Collections:||Molecular and Biomedical Science publications|
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