The Structural hallmarks of integrin activation are:Ī) complete extension of the extracellular domains andī) separation of the cytoplasmic leg domains (structural rearrangements detailed in ). This low affinity structure undergoes rapid, reversible conformational changes to increase ligand affinity, termed “activation” (reviewed in ). Crystal structures have revealed that integrin heterodimers, occur in an inactive, bent V-shape with the head close to the membrane-proximal regions of the legs, maintained by the α/β salt bridge at the inner membrane region and helix packing of the transmembrane (TM) region. Structural and functional studies suggest that integrins can exist in different ligand affinity states – low, intermediate and high (reviewed in ). Integrin activation is an important mechanism through which cells regulate integrin function by manipulating the ligand affinity of integrins spatially and temporally.
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