Structural Aspects of Integrins

Abstract

Structural studies on integrins have recently made great strides in recent years. Crystal structures of the complete extracellular fragments of three integrins in open and closed conformations, 6 a-I domains in complex with ligands, and at least 20 intracellular proteins in complex with cytosolic tails have been obtained; and several transmembrane and cytosolic complexes have been determined by NMR. High resolution EM studies complement these atomic resolution techniques by studying the integrin in different activation states. Although we still have only a few experimental examples among integrin family members, the high level of sequence homology between integrins means that reliable models can be built for the other members of the integrin family. These structures make sense of a lot of preceding biochemical, biophysical and mutagenesis studies, and generate many new testable hypotheses of integrin function. This chapter emphasizes new structural insights applicable to all integrins, with an emphasis on those integrins that contain an a-I domain. The structural data reinforce the notion of the integrin as a molecule in dynamic equilibrium at the cell surface, regulated by binding both to extracellular and intracellular ligands.