Full-length αIIbβ3 CryoEM structure reveals intact integrin initiate-activation intrinsic architecture.

ABSTRACT: Integrin αIIbβ3 is the key receptor regulating platelet retraction and accumulation, thus pivotal for hemostasis, and arterial thrombosis as well as a proven drug-target for antithrombotic therapies. Here we resolve the cryoEM structures of the intact full-length αIIbβ3, which covers three distinct states along the activation pathway. Here, we resolve intact αIIbβ3 structure at 3Å resolution, revealing the overall topology of the heterodimer with the transmembrane (TM) helices and the head region ligand-binding domain tucked in a specific angle proximity to the TM region. In response to the addition of an Mn²⁺ agonist, we resolved two coexisting states, "intermediate" and "pre-active". Our structures show conformational changes of the intact αIIbβ3 activating trajectory, as well

SUBMITTER: Wang Z 

PROVIDER: S-EPMC9980189 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature