title: The modular serine proteases of the complement cascade.
abstract: Modular serine proteases are central to the complement cascade of the mammalian humoral immune system. These proteases form protein complexes through multi-domain interactions to achieve their proteolytic activity. We review the structural insights into complement initiation by auto-activation of the hetero-tetrameric proteases of the large danger-recognition protein complexes, amplification and labelling of particles by the formation and activity of C3 convertases, and regulation by convertase dissociation and degradation to prevent 'bystander' damage to healthy host cells and tissues. The data reveal that complex formation and large domain-domain rearrangements underlie the proteolytic reactions of the complement cascade, which enables the host to recognize and clear invading microbes and host debris from its blood and fluids surrounding tissues.
authors.affiliation: Crystal and Structural Chemistry, Bijvoet Center for Biomolecular Research, Department of Chemistry, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands.
authors.forename: Federico
authors.initials: F
authors.lastname: Forneris
authors.forename: Jin
authors.initials: J
authors.lastname: Wu
authors.forename: Piet
authors.initials: P
authors.lastname: Gros
mesh_terms: D000818:Animals; D003167:Complement Activation / Q000502:physiology; D050577:Complement C3-C5 Convertases / Q000737:chemistry / Q000378:metabolism; D003165:Complement System Proteins / Q000737:chemistry / Q000378:metabolism*; D004789:Enzyme Activation; D006801:Humans; D008954:Models, Biological; D008958:Models, Molecular; D011487:Protein Conformation; D057057:Serine Proteases / Q000737:chemistry / Q000378:metabolism*
chemical_list: D003165:Complement System Proteins; D057057:Serine Proteases; D050577:Complement C3-C5 Convertases