Structural basis of prothrombin recognition by a Type-I anti-prothrombin antiphospholipid antibody revealed by cryo-EM

Suresh Kumar, Ph.D.
Saint Louis University
St. Louis, MO, U.S.

Antiprothrombin (anti-PT) antibodies are found in antiphospholipid patients, but their interaction with prothrombin is unclear. Prothrombin adopts closed and open forms. The authors discovered Type- I and Type-II antibodies and proposed that Type-I recognize the open form and through this study report the discovery, structural and functional characterization in human plasma of a Type-I antibody, POmAb. 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 centered at residues R90-Y93. The authors also discuss studies that reveal the structural basis of prothrombin recognition by a Type-I antiphospholipid antibody and uncover an exciting new strategy to achieve anticoagulation in human plasma.