Early complement proteases: C1r, C1s and MASPs. A structural insight into activation and functions.
C1r, C1s and the mannose-binding lectin-associated serine proteases (MASPs) are responsible for the initiation of the classical- and lectin pathway activation of the complement system. These enzymes do not act alone, but form supramolecular complexes with pattern recognition molecules such as C1q, MBL, and ficolins. They share the same domain organization but have different substrate specificities and fulfill different physiological functions. In the recent years the rapid progress of structural biology facilitated the understanding of the molecular mechanism of complement activation at atomic level. In this review we summarize our current knowledge about the structure and function of the early complement proteases, delineate the latest models of the multimolecular complexes and present the functional consequences inferred from the structural studies. We also discuss some open questions and debated issues that need to be resolved in the future.
Gál
Péter
P
Institute of Enzymology, Biological Research Center, Hungarian Academy of Sciences, Budapest, Hungary. gal@enzim.hu
Dobó
József
J
Závodszky
Péter
P
Sim
Robert B M
RB
D000818:Animals; D003167:Complement Activation / Q000276:immunology; D015923:Complement C1r / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D003173:Complement C1s / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D004789:Enzyme Activation; D006801:Humans; D050606:Mannose-Binding Protein-Associated Serine Proteases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation
D050606:Mannose-Binding Protein-Associated Serine Proteases; D015923:Complement C1r; D003173:Complement C1s