Year: 2026
Type: article
Abstract: PURPOSE OF REVIEW: Cryogenic electron microscopy (cryo-EM) resolves the structures of proteins and their complexes under near-native conditions that are often inaccessible to other structural techniques. Cryo-EM has recently contributed significant advances in basic knowledge to the field of coagulation. New paradigms regarding individual domain role in protein-protein interactions have emerged, casting the main reactions of the coagulation cascade in a much-needed structural context. This review focuses on recent advances in the study of coagulation factors using cryo-EM. RECENT FINDINGS: Cryo-EM structures have defined the architecture of Factor V/Va free and bound to their biological partners, revealing that protease domains dominate protein-protein interactions while auxiliary domains act as scaffolds. Breakthroughs in mapping autoantibody epitopes for prothrombin and Factor VIII have elucidated pathogenic mechanisms in antiphospholipid syndrome and hemophilia. Furthermore, cryo-EM is accelerating biotherapeutic design, evidenced by recent structures of Factor XIIa, prothrombin and engineered Factor VIII. SUMMARY: Cryo-EM, often, enables the resolution of discrete macromolecular conformations using minimal quantities of full-length proteins. These structural insights enable the rational design of next-generation therapeutics and targeted diagnostics guided by near physiological forms, marking a new era in coagulation research. Future integration with HDX-MS, smFRET, and cryo-electron tomography (cryo-ET) will resolve these molecular machineries in situ on the surface of activated platelets and vascular beds.
Source: Current Opinion in Hematology
Institution: Saint Louis University
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: Structural Studies of Beta-2 glycoprotein I in the Antiphospholipid Syndrome, Structural basis of prothrombin activation, Structural enzymology of factor V activation, Structural enzymology of protein C, Introducing NanoProTEN, a novel approach for anticoagulation in patients with prothrombotic autoantibodies
OpenAlex ID: W7161375753