2BRQ: Crystal Structure Of The Filamin A Repeat 21 Complexed With The Integrin Beta7 Cytoplasmic Tail Peptide

Citation:
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.
PDB ID: 2BRQDownload
MMDB ID: 37569
PDB Deposition Date: 2005/5/11
Updated in MMDB: 2007/12
Experimental Method:
x-ray diffraction
Resolution: 2.1  Å
Source Organism:
Similar Structures:
Biological Unit for 2BRQ: tetrameric; determined by author and by software (PISA)
Molecular Components in 2BRQ
Label Count Molecule
Proteins (4 molecules)
2
Filamin a(Gene symbol: FLNA)
Molecule annotation
2
Integrin Beta-7 Subunit(Gene symbol: ITGB7)
Molecule annotation
Chemicals (4 molecules)
1
2
2
2
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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