The human platelet antigen-1b (Pro³³) variant of α_IIbβ₃ allosterically shifts the dynamic conformational equilibrium of this integrin toward the active state.

ABSTRACT: Integrins are heterodimeric cell-adhesion receptors comprising α and β subunits that transmit signals allosterically in both directions across the membrane by binding to intra- and extracellular components. The human platelet antigen-1 (HPA-1) polymorphism in α_IIbβ₃ arises from a Leu → Pro exchange at residue 33 in the genu of the β₃ subunit, resulting in Leu³³ (HPA-1a) or Pro³³ (HPA-1b) isoforms. Although clinical investigations have provided conflicting results, some studies have suggested that Pro³³ platelets exhibit increased thrombogenicity. Under flow-dynamic conditions, the Pro³³ variant displays prothrombotic properties, characterized by increased platelet adhesion, aggregate/thrombus formation, and outsid

SUBMITTER: Pagani G 

PROVIDER: S-EPMC5880125 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature