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Structural insight into proteolytic activation and regulation of the complement system
Author(s) -
SchatzJakobsen Janus A.,
Pedersen Dennis V.,
Andersen Gregers R.
Publication year - 2016
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1111/imr.12465
Subject(s) - complement system , effector , complement (music) , alternative complement pathway , biology , microbiology and biotechnology , proteolytic enzymes , computational biology , structural biology , activator (genetics) , biochemistry , enzyme , immunology , immune system , receptor , gene , complementation , phenotype
Summary The complement system is a highly complex and carefully regulated proteolytic cascade activated through three different pathways depending on the activator recognized. The structural knowledge regarding the intricate proteolytic enzymes that activate and control complement has increased dramatically over the last decade. This development has been pivotal for understanding how mutations within complement proteins might contribute to pathogenesis and has spurred new strategies for development of complement therapeutics. Here we describe and discuss the complement system from a structural perspective and integrate the most recent findings obtained by crystallography, small‐angle X‐ray scattering, and electron microscopy. In particular, we focus on the proteolytic enzymes governing activation and their products carrying the biological effector functions. Additionally, we present the structural basis for some of the best known complement inhibitors. The large number of accumulated molecular structures enables us to visualize the relative size, position, and overall orientation of many of the most interesting complement proteins and assembled complexes on activator surfaces and in membranes.