title: Complement System Part I - Molecular Mechanisms of Activation and Regulation.
abstract: Complement is a complex innate immune surveillance system, playing a key role in defense against pathogens and in host homeostasis. The complement system is initiated by conformational changes in recognition molecular complexes upon sensing danger signals. The subsequent cascade of enzymatic reactions is tightly regulated to assure that complement is activated only at specific locations requiring defense against pathogens, thus avoiding host tissue damage. Here, we discuss the recent advances describing the molecular and structural basis of activation and regulation of the complement pathways and their implication on physiology and pathology. This article will review the mechanisms of activation of alternative, classical, and lectin pathways, the formation of C3 and C5 convertases, the action of anaphylatoxins, and the membrane-attack-complex. We will also discuss the importance of structure-function relationships using the example of atypical hemolytic uremic syndrome. Lastly, we will discuss the development and benefits of therapies using complement inhibitors.
authors.affiliation: UMR_S 1138, Cordeliers Research Center, Complement and Diseases Team, INSERM , Paris , France ; UMR_S 1138, Centre de Recherche des Cordeliers, Sorbonne Paris Cité, Université Paris Descartes , Paris , France ; UMR_S 1138, Centre de Recherche des Cordeliers, Sorbonne Universités, Université Pierre et Marie Curie-Paris , Paris , France.
authors.forename: Nicolas S
authors.initials: NS
authors.lastname: Merle
authors.affiliation: UMR_S 1138, Centre de Recherche des Cordeliers, Sorbonne Paris Cité, Université Paris Descartes , Paris , France ; UMR_S 1138, Centre de Recherche des Cordeliers, Sorbonne Universités, Université Pierre et Marie Curie-Paris , Paris , France ; UMR_S 1138, Cordeliers Research Center, Integrative Cancer Immunology Team, INSERM , Paris , France.
authors.forename: Sarah Elizabeth
authors.initials: SE
authors.lastname: Church
authors.affiliation: UMR_S 1138, Cordeliers Research Center, Complement and Diseases Team, INSERM , Paris , France ; UMR_S 1138, Centre de Recherche des Cordeliers, Sorbonne Paris Cité, Université Paris Descartes , Paris , France ; UMR_S 1138, Centre de Recherche des Cordeliers, Sorbonne Universités, Université Pierre et Marie Curie-Paris , Paris , France ; Service d'Immunologie Biologique, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges-Pompidou , Paris , France.
authors.forename: Veronique
authors.initials: V
authors.lastname: Fremeaux-Bacchi
authors.affiliation: UMR_S 1138, Cordeliers Research Center, Complement and Diseases Team, INSERM , Paris , France ; UMR_S 1138, Centre de Recherche des Cordeliers, Sorbonne Paris Cité, Université Paris Descartes , Paris , France ; UMR_S 1138, Centre de Recherche des Cordeliers, Sorbonne Universités, Université Pierre et Marie Curie-Paris , Paris , France.
authors.forename: Lubka T
authors.initials: LT
authors.lastname: Roumenina
keywords: alternative complement pathway; anaphylatoxins; classical complement pathway; complement regulatory proteins; complement system proteins; endothelial cells; membrane-attack-complex; structure–function relationships