New insight into the traditional model of the coagulation cascade and its regulation: illustrated review of a three-dimensional view

Res Pract Thromb Haemost. 2023 Aug 7;7(6):102160. doi: 10.1016/j.rpth.2023.102160. eCollection 2023 Aug.ABSTRACTThe coagulation process relies on an intricate network of three-dimensional structural interactions and subtle biological regulations. In the present review, we illustrate the state of the art of the structural biology of the coagulation cascade by surveying the Protein Data Bank and the EBI AlphaFold databases. Investigations performed in the last decade have provided structural information on essentially all players involved in the process. Indeed, the initial characterization of specific and rather canonical domains has been progressively extended to complicated multidomain proteins. Recently, the application of cryogenic electron microscopy techniques has unraveled the structural features of highly complex coagulation factors, which has led to enhanced understanding. This review initially focuses on the structure of the individual factors as a function of their involvement in intrinsic, extrinsic, and common pathways. A specific emphasis is given to what is known or unknown on the structural basis of each step of the cascade. Available data providing clues on the structural recognition of the factors involved in the functional partnerships of the pathways are illustrated. Recent structures of important complexes formed by these proteins with regulators are described, focusing on the drugs used as anticoagulants and on their reversal agents. Finally, we highlight...
Source: Thrombosis and Haemostasis - Category: Hematology Authors: Source Type: research