title: A structural mechanism of integrin alpha(IIb)beta(3) "inside-out" activation as regulated by its cytoplasmic face.
abstract: Activation of the ligand binding function of integrin heterodimers requires transmission of an "inside-out" signal from their small intracellular segments to their large extracellular domains. The structure of the cytoplasmic domain of a prototypic integrin alpha(IIb)beta(3) has been solved by NMR and reveals multiple hydrophobic and electrostatic contacts within the membrane-proximal helices of its alpha and the beta cytoplasmic tails. The interface interactions are disrupted by point mutations or the cytoskeletal protein talin that are known to activate the receptor. These results provide a structural mechanism by which a handshake between the alpha and the beta cytoplasmic tails restrains the integrin in a resting state and unclasping of this interaction triggers the inside-out conformational signal that leads to receptor activation.
authors.affiliation: Structural Biology Program, Cleveland, OH 44195, USA.
authors.forename: Olga
authors.initials: O
authors.lastname: Vinogradova
authors.forename: Algirdas
authors.initials: A
authors.lastname: Velyvis
authors.forename: Asta
authors.initials: A
authors.lastname: Velyviene
authors.forename: Bin
authors.initials: B
authors.lastname: Hu
authors.forename: Thomas
authors.initials: T
authors.lastname: Haas
authors.forename: Edward
authors.initials: E
authors.lastname: Plow
authors.forename: Jun
authors.initials: J
authors.lastname: Qin
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003593:Cytoplasm / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000737:chemistry*; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D016608:Talin / Q000494:pharmacology
chemical_list: D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D016608:Talin