Di Cera Enrico, Mohammed Bassem M, Pelc Leslie A, Stojanovski Bosko M
Edward A. Doisy Department of Biochemistry and Molecular Biology Saint Louis University School of Medicine St. Louis Missouri USA.
Res Pract Thromb Haemost. 2022 Nov 2;6(7):e12830. doi: 10.1002/rth2.12830. eCollection 2022 Oct.
A State of the Art lecture titled "Cryo-EM structures of coagulation factors" was presented at the ISTH Congress in 2022. Cryogenic electron microscopy (cryo-EM) is a revolutionary technique capable of solving the structure of high molecular weight proteins and their complexes, unlike nuclear magnetic resonance (NMR), and under conditions not biased by crystal contacts, unlike X-ray crystallography. These features are particularly relevant to the analysis of coagulation factors that are too big for NMR and often recalcitrant to X-ray investigation. Using cryo-EM, we have solved the structures of coagulation factors V and Va, prothrombinase on nanodiscs, and the prothrombin-prothrombinase complex. These structures have advanced basic knowledge in the field of thrombosis and hemostasis, especially on the function of factor V and the molecular mechanism for prothrombin activation, and set the stage for exciting new lines of investigation. Finally, we summarize relevant new data on this topic presented during the 2022 ISTH Congress.
一场题为“凝血因子的冷冻电镜结构”的前沿讲座于2022年在国际血栓与止血学会（ISTH）大会上发表。低温电子显微镜（cryo-EM）是一项革命性技术，与核磁共振（NMR）不同，它能够解析高分子量蛋白质及其复合物的结构，并且与X射线晶体学不同，它不受晶体接触的影响。这些特性对于分析因分子量太大而无法用NMR研究且通常难以用X射线进行研究的凝血因子尤为重要。利用冷冻电镜，我们解析了凝血因子V和Va、纳米盘上的凝血酶原酶以及凝血酶原-凝血酶原酶复合物的结构。这些结构推进了血栓形成和止血领域的基础知识，特别是关于因子V的功能以及凝血酶原激活的分子机制，并为令人兴奋的新研究方向奠定了基础。最后，我们总结了在2022年ISTH大会期间发表的关于该主题的相关新数据。
