Integrins are cell adhesion molecules that play important roles in many biological processes including hemostasis, immune responses, development, and cancer. Their adhesiveness is dynamically regulated through a process termed inside-out signaling. In addition, ligand binding transduces outside-in signals from the extracellular domain to the cytoplasm. Advances in the past several years have shed light on structural basis for integrin regulation and signaling, especially how the large-scale reorientations of the ectodomain are related to the inter-domain and intra-domain shape shifting that changes ligand-binding affinity. Experiments have also shown how the conformational changes of the ectodomain are linked to changes in the α- and β-subunit transmembrane and cytoplasmic domains.
