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C4b-binding protein: The good, the bad and the deadly. Novel functions of an old friend.

Ermert, David LU and Blom, Anna LU (2016) In Immunology Letters 169. p.82-92
Abstract
C4b-binding protein (C4BP) is best known as a potent soluble inhibitor of the classical and lectin pathways of the complement system. This large 500kDa multimeric plasma glycoprotein is expressed mainly in the liver but also in lung and pancreas. It consists of several identical 75kDa α-chains and often also one 40kDa β-chain, both of which are mainly composed of complement control protein (CCP) domains. Structure-function studies revealed that one crucial binding site responsible for inhibition of complement is located to CCP1-3 of the α-chain. Binding of anticoagulant protein S to the CCP1 of the β-chain provides C4BP with the ability to strongly bind apoptotic and necrotic cells in order to prevent inflammation arising from activation... (More)
C4b-binding protein (C4BP) is best known as a potent soluble inhibitor of the classical and lectin pathways of the complement system. This large 500kDa multimeric plasma glycoprotein is expressed mainly in the liver but also in lung and pancreas. It consists of several identical 75kDa α-chains and often also one 40kDa β-chain, both of which are mainly composed of complement control protein (CCP) domains. Structure-function studies revealed that one crucial binding site responsible for inhibition of complement is located to CCP1-3 of the α-chain. Binding of anticoagulant protein S to the CCP1 of the β-chain provides C4BP with the ability to strongly bind apoptotic and necrotic cells in order to prevent inflammation arising from activation of complement by these cells. Further, C4BP interacts strongly with various types of amyloid and enhances fibrillation of islet amyloid polypeptide secreted from pancreatic beta cells, which may attenuate pro-inflammatory and cytotoxic effects of this amyloid. Full deficiency of C4BP has not been identified but non-synonymous alterations in its sequence have been found in haemolytic uremic syndrome and recurrent pregnancy loss. Furthermore, C4BP is bound by several bacterial pathogens, notably Streptococcus pyogenes, which due to inhibition of complement and enhancement of bacterial adhesion to endothelial cells provides these bacteria with a survival advantage in the host. Thus, depending on the context, C4BP has a protective or detrimental role in the organism. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Immunology Letters
volume
169
pages
82 - 92
publisher
Elsevier
external identifiers
  • pmid:26658464
  • scopus:84949908683
  • wos:000369205200010
ISSN
0165-2478
DOI
10.1016/j.imlet.2015.11.014
language
English
LU publication?
yes
id
ba1e9f95-5580-492f-b989-0b0973710d7a (old id 8505131)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/26658464?dopt=Abstract
date added to LUP
2016-01-12 12:23:26
date last changed
2017-11-19 04:19:12
@article{ba1e9f95-5580-492f-b989-0b0973710d7a,
  abstract     = {C4b-binding protein (C4BP) is best known as a potent soluble inhibitor of the classical and lectin pathways of the complement system. This large 500kDa multimeric plasma glycoprotein is expressed mainly in the liver but also in lung and pancreas. It consists of several identical 75kDa α-chains and often also one 40kDa β-chain, both of which are mainly composed of complement control protein (CCP) domains. Structure-function studies revealed that one crucial binding site responsible for inhibition of complement is located to CCP1-3 of the α-chain. Binding of anticoagulant protein S to the CCP1 of the β-chain provides C4BP with the ability to strongly bind apoptotic and necrotic cells in order to prevent inflammation arising from activation of complement by these cells. Further, C4BP interacts strongly with various types of amyloid and enhances fibrillation of islet amyloid polypeptide secreted from pancreatic beta cells, which may attenuate pro-inflammatory and cytotoxic effects of this amyloid. Full deficiency of C4BP has not been identified but non-synonymous alterations in its sequence have been found in haemolytic uremic syndrome and recurrent pregnancy loss. Furthermore, C4BP is bound by several bacterial pathogens, notably Streptococcus pyogenes, which due to inhibition of complement and enhancement of bacterial adhesion to endothelial cells provides these bacteria with a survival advantage in the host. Thus, depending on the context, C4BP has a protective or detrimental role in the organism.},
  author       = {Ermert, David and Blom, Anna},
  issn         = {0165-2478},
  language     = {eng},
  pages        = {82--92},
  publisher    = {Elsevier},
  series       = {Immunology Letters},
  title        = {C4b-binding protein: The good, the bad and the deadly. Novel functions of an old friend.},
  url          = {http://dx.doi.org/10.1016/j.imlet.2015.11.014},
  volume       = {169},
  year         = {2016},
}