Complement driven by conformational changes.
Complement in mammalian plasma recognizes pathogenic, immunogenic and apoptotic cell surfaces, promotes inflammatory responses and marks particles for cell lysis, phagocytosis and B-cell stimulation. At the heart of the complement system are two large proteins, complement component C3 and protease factor B. These two proteins are pivotal for amplification of the complement response and for labelling of the target particles, steps that are required for effective clearance of the target. Here we review the molecular mechanisms of complement activation, in which proteolysis and complex formation result in large conformational changes that underlie the key offensive step of complement executed by C3 and factor B. Insights into the mechanisms of complement amplification are crucial for understanding host defence and pathogen immune evasion, and for the development of complement-immune therapies.
Crystal and Structural Chemistry, Bijvoet Center for Biomolecular Research, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, Netherlands. p.gros@uu.nl
Piet
P
Gros
Fin J
FJ
Milder
Bert J C
BJ
Janssen
D000818:Animals; D003167:Complement Activation / Q000276:immunology*; D003176:Complement C3 / Q000276:immunology*; D011415:Complement Factor B / Q000276:immunology*; D006801:Humans
D003176:Complement C3; D011415:Complement Factor B