Effects of limiting extension at the alphaIIb genu on ligand binding to integrin alphaIIbbeta3.

ABSTRACT: Structural data of integrin alphaIIbbeta3 have been interpreted as supporting a model in which: 1) the receptor exists primarily in a "bent," low affinity conformation on unactivated platelets and 2) activation induces an extended, high affinity conformation prior to, or following, ligand binding. Previous studies found that "clasping" the alphaIIb head domain to the beta3 tail decreased fibrinogen binding. To study the role of alphaIIb extension about the genu, we introduced a disulfide "clamp" between the alphaIIb thigh and calf-1 domains. Clamped alphaIIbbeta3 had markedly reduced ability to bind the large soluble ligands fibrinogen and PAC-1 when activated with monoclonal antibody (mAb) PT25-2 but not when activated by Mn(2+) or by coexpressing the clamped alphaIIb with a beta3 subunit

SUBMITTER: Blue R 

PROVIDER: S-EPMC2878525 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature