title: Structural basis of integrin regulation and signaling.
abstract: Integrins are cell adhesion molecules that mediate cell-cell, cell-extracellular matrix, and cell-pathogen interactions. They play critical roles for the immune system in leukocyte trafficking and migration, immunological synapse formation, costimulation, and phagocytosis. Integrin adhesiveness can be dynamically regulated through a process termed inside-out signaling. In addition, ligand binding transduces signals from the extracellular domain to the cytoplasm in the classical outside-in direction. Recent structural, biochemical, and biophysical studies have greatly advanced our understanding of the mechanisms of integrin bidirectional signaling across the plasma membrane. Large-scale reorientations of the ectodomain of up to 200 A couple to conformational change in ligand-binding sites and are linked to changes in alpha and beta subunit transmembrane domain association. In this review, we focus on integrin structure as it relates to affinity modulation, ligand binding, outside-in signaling, and cell surface distribution dynamics.
authors.affiliation: The CBR Institute for Biomedical Research, Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA. luo@cbr.med.harvard.edu
authors.forename: Bing-Hao
authors.initials: BH
authors.lastname: Luo
authors.forename: Christopher V
authors.initials: CV
authors.lastname: Carman
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Springer
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000235:genetics / Q000276:immunology; D002465:Cell Movement / Q000235:genetics / Q000276:immunology*; D005109:Extracellular Matrix / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D006801:Humans; D016023:Integrins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D007962:Leukocytes / Q000166:cytology / Q000276:immunology*; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D017434:Protein Structure, Tertiary; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D013329:Structure-Activity Relationship
chemical_list: D016023:Integrins