[HTML][HTML] A structural mechanism of integrin αIIbβ3 “inside-out” activation as regulated by its cytoplasmic face

O Vinogradova, A Velyvis, A Velyviene, B Hu, TA Haas… - Cell, 2002 - cell.com
O Vinogradova, A Velyvis, A Velyviene, B Hu, TA Haas, EF Plow, J Qin
Cell, 2002cell.com
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 α IIb β 3 has been solved by
NMR and reveals multiple hydrophobic and electrostatic contacts within the membrane-
proximal helices of its α and the β cytoplasmic tails. The interface interactions are disrupted
by point mutations or the cytoskeletal protein talin that are known to activate the receptor …
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 αIIbβ3 has been solved by NMR and reveals multiple hydrophobic and electrostatic contacts within the membrane-proximal helices of its α and the β 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 α and the β 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.
cell.com