Cryo-EM structure and functional basis of prothrombin recognition by a type I antiprothrombin antiphospholipid antibody.

ABSTRACT:

Abstract

Antiprothrombin antibodies are found in antiphospholipid patients, but how they interact with prothrombin remains elusive. Prothrombin adopts closed and open forms. We recently discovered type I and type II antibodies and proposed that type I recognizes the open form. In this study, we report the discovery and structural and functional characterization in human plasma of a type I antibody, POmAb (prothrombin open monoclonal antibody). Using surface plasmon resonance and single-molecule spectroscopy, we show that POmAb interacts with kringle-1 of prothrombin, shifting the equilibrium toward the open form. Using single-particle cryogenic electron microscopy (cryo-EM), we establish that the epitope targeted by POmAb is in kringle-1, comprising an extended binding interface ce

SUBMITTER: Kumar S 

PROVIDER: S-EPMC11103173 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature