Crystalizing our view of the contact system

摘要

How does the contact activation system (CAS) assemble on cellular surfaces? Although researchers have been studying the contact factors prekallikrein (PK), high-molecular-weight kininogen (HK), and factor XII (FXII), and their respective roles in inflammation, immunity, and coagulation for over half a century, we now get some clarity on a quaternary structure for this fascinating multienzyme complex. In this issue of Blood, Kaira and colleagues describe the first crystal structure of an FXII domain in complex with a putative receptor, and they propose a model by which this binding protein, the globular complement C1q receptor (gC1qR), can act as a chaperone to cluster contact factors together prior to initiating factor XI (FXI)-dependent blood coagulation and inflammatory bradykinin (BK) liberation.(1)