Structural and functional features of factor XI

Authors


David Gailani, Division of Hematology/Oncology, Vanderbilt University, 777 Preston Research Building, 2220 Pierce Ave, Nashville, TN 37232-6307, USA.
Tel.: +1 615 936 1505; fax: +1 615 343 8420.
E-mail: dave.gailani@vanderbilt.edu

Abstract

Summary.  Factor XI (FXI) has structural and mechanistic features that distinguish it from other coagulation proteases. A relatively recent addition to vertebrate plasma coagulation, FXI is a homodimer, with each subunit containing four apple domains and a protease domain. The apple domains form a disk structure with binding sites for platelets, high molecular weight kininogen, and the substrate factor IX (FIX). FXI is converted to the active protease FXIa by cleavage of the Arg369−Ile370 bond on each subunit. This converts the catalytic domains to the active forms, and unmasks exosites on the apple domains required for FIX binding. FXI activation by factor XIIa or thrombin proceeds through an intermediate with only one activated submit (1/2-FXIa). 1/2-FXIa activates FIX in a similar manner to FXIa. While the importance of the homodimeric structure of FXI is not certain, it may represent a strategy for binding to FIX and a platelet surface simultaneously.

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