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.
Original language | English |
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Pages (from-to) | 337-47 |
Number of pages | 11 |
Journal | Molecular Cell |
Volume | 21 |
Issue number | 3 |
DOIs | |
Publication status | Published - 3 Feb 2006 |
Keywords
- Amino Acid Sequence
- Animals
- Binding Sites
- Calpain
- Contractile Proteins
- Crystallography, X-Ray
- Filamins
- Integrin beta Chains
- Mice
- Microfilament Proteins
- Models, Molecular
- Molecular Sequence Data
- NIH 3T3 Cells
- Nuclear Magnetic Resonance, Biomolecular
- Protein Binding
- Protein Conformation
- Protein Structure, Tertiary
- Recombinant Fusion Proteins
- Reproducibility of Results
- Sequence Homology, Amino Acid
- Talin