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RESEARCH PRODUCT
The molecular basis of filamin binding to integrins and competition with talin.
Pengju JiangIain D. CampbellJari YlänneJari YlänneCamilla L. OxleyYatish LadMassimiliano BaldassarreKate L. WegenerDavid A. CalderwoodTiila R. Kiemasubject
Models MolecularTalinanimal structuresIntegrin beta ChainsProtein ConformationFilaminsRecombinant Fusion ProteinsIntegrinMolecular Sequence Datamacromolecular substancesPlasma protein bindingFilaminCrystallography X-RayFilamin bindingMiceContractile ProteinsFLNAAnimalsAmino Acid SequenceMolecular BiologyNuclear Magnetic Resonance BiomolecularBinding SitesbiologySequence Homology Amino AcidCalpainMicrofilament ProteinsReproducibility of ResultsCell BiologyActin cytoskeletonCell biologyProtein Structure Tertiarybody regionsIntegrin alpha Mbiology.proteinNIH 3T3 CellsIntegrin beta 6Protein Bindingdescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2006-02-01 | Molecular cell |