Structural insight into proteolytic activation and regulation of the complement system

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 dram...

Full description

Saved in:
Bibliographic Details
Published in:Immunological reviews 2016-11, Vol.274 (1), p.59-73
Main Authors: Schatz-Jakobsen, Janus A., Pedersen, Dennis V., Andersen, Gregers R.
Format: Article
Language:English
Subjects:
Animals
complement
Complement Activation
Complement Inactivating Agents - therapeutic use
Complement System Proteins - genetics
Complement System Proteins - immunology
Humans
immune disorders
Immune System Diseases - genetics
Immune System Diseases - immunology
Immune System Diseases - therapy
Multiprotein Complexes - metabolism
Mutation - genetics
Proteolysis
proteolytic cascade
structural biology
Structure-Activity Relationship
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0105-2896
1600-065X
DOI:10.1111/imr.12465