2BRQ

Crystal structure of the filamin A repeat 21 complexed with the integrin beta7 cytoplasmic tail peptide

Summary for 2BRQ

• Entry DOI: 10.2210/pdb2brq/pdb
• Related: 2BP3
• Descriptor: FILAMIN A, INTEGRIN BETA-7 SUBUNIT, GLUTATHIONE, ... (5 entities in total)
• Functional Keywords: structural protein, cytoskeleton-complex, actin-binding, cytoskeleton, immunoglobulin like, integrin, cell adhesion
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Cytoplasm, cell cortex: P21333; Membrane; Single-pass type I membrane protein: P26010
• Total number of polymer chains: 4
• Total formula weight: 27834.66

Authors

Kiema, T.-R.,Ylanne, J. (deposition date: 2005-05-11, release date: 2006-02-07, Last modification date: 2023-12-13)

Primary citation

Kiema, T.,Lad, Y.,Jiang, P.,Oxley, C.L.,Baldassarre, M.,Wegener, K.L.,Campbell, I.D.,Ylanne, J.,Calderwood, D.A.
The Molecular Basis of Filamin Binding to Integrins and Competition with Talin.
Mol.Cell, 21:337-, 2006

PubMed 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 beta cytoplasmic tail forms an extended beta strand that interacts with beta 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.

PubMed: 16455489
DOI: 10.1016/J.MOLCEL.2006.01.011

Experimental method

X-RAY DIFFRACTION (2.1 Å)