Structure of an integrin alphaIIb beta3 transmembrane-cytoplasmic heterocomplex provides insight into integrin activation.

ABSTRACT: Heterodimeric integrin adhesion receptors regulate diverse biological processes including angiogenesis, thrombosis and wound healing. The transmembrane-cytoplasmic domains (TMCDs) of integrins play a critical role in controlling activation of these receptors via an inside-out signaling mechanism, but the precise structural basis remains elusive. Here, we present the solution structure of integrin alphaIIb beta3 TMCD heterodimer, which reveals a right-handed coiled-coil conformation with 2 helices intertwined throughout the transmembrane region. The helices extend into the cytoplasm and form a clasp that differs significantly from a recently published alphaIIb beta3 TMCD structure. We show that while a point mutation in the clasp interface modestly activates alphaIIb beta3, additional mutat

SUBMITTER: Yang J 

PROVIDER: S-EPMC2764936 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature