A novel interaction between complement inhibitor C4b-binding protein and plasminogen that enhances plasminogen activation.
Agarwal, Vaibhav LU ; Talens, Simone LU ; Grandits, Alexander M and Blom, Anna LU
(2015)
In Journal of Biological Chemistry
290(30).
p.18333-18342
- Abstract
- The complement, coagulation and fibrinolytic systems are crucial for the maintenance of tissue homeostasis. To date numerous interactions and cross talks have been identified between these cascades. In line with this, here we propose a novel, hitherto unknown interaction between the complement inhibitor C4b-binding protein (C4BP) and plasminogen of the fibrinolytic pathway. Binding of C4BP to S. pneumoniae is a known virulence mechanism of this pathogen and it was increased in the presence of plasminogen. Interestingly, the acute phase variant of C4BP lacking the β-chain and protein S binds plasminogen much stronger than the main isoform containing the β-chain and protein S. Indeed, the complement control protein (CCP) 8 domain of C4BP,... (More)
- The complement, coagulation and fibrinolytic systems are crucial for the maintenance of tissue homeostasis. To date numerous interactions and cross talks have been identified between these cascades. In line with this, here we propose a novel, hitherto unknown interaction between the complement inhibitor C4b-binding protein (C4BP) and plasminogen of the fibrinolytic pathway. Binding of C4BP to S. pneumoniae is a known virulence mechanism of this pathogen and it was increased in the presence of plasminogen. Interestingly, the acute phase variant of C4BP lacking the β-chain and protein S binds plasminogen much stronger than the main isoform containing the β-chain and protein S. Indeed, the complement control protein (CCP) 8 domain of C4BP, which would otherwise be sterically hindered by the β-chain, primarily mediates this interaction. Moreover, the lysine-binding sites in plasminogen kringle domains facilitate the C4BP-plasminogen interaction. Furthermore, C4BP readily forms complexes with plasminogen in fluid phase and such complexes are present in human serum and plasma. Importantly, while the presence of plasminogen did not affect the factor I cofactor activity of C4BP, the activation of plasminogen by urokinase-type plasminogen activator to active plasmin was significantly augmented in the presence of C4BP. Taken together, our data demonstrate a novel interaction between two proteins of the complement and fibrinolytic system. Most complexes might be formed during the acute phase of inflammation and have an effect on the homeostasis at the site of injury or acute inflammation. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/7486801
- author
- Agarwal, Vaibhav
LU
; Talens, Simone
LU
; Grandits, Alexander M
and Blom, Anna
LU
- organization
- publishing date
- 2015
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Biological Chemistry
- volume
- 290
- issue
- 30
- pages
- 18333 - 18342
- publisher
- American Society for Biochemistry and Molecular Biology
- external identifiers
-
- pmid:26067271
- wos:000358512100007
- scopus:84937773394
- pmid:26067271
- ISSN
- 1083-351X
- DOI
- 10.1074/jbc.M114.619494
- language
- English
- LU publication?
- yes
- id
- 5e16ff07-43f5-45d9-845f-f59dd79a1ea5 (old id 7486801)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/26067271?dopt=Abstract
- date added to LUP
- 2016-04-01 10:05:11
- date last changed
- 2022-04-19 22:28:18
@article{5e16ff07-43f5-45d9-845f-f59dd79a1ea5,
abstract = {{The complement, coagulation and fibrinolytic systems are crucial for the maintenance of tissue homeostasis. To date numerous interactions and cross talks have been identified between these cascades. In line with this, here we propose a novel, hitherto unknown interaction between the complement inhibitor C4b-binding protein (C4BP) and plasminogen of the fibrinolytic pathway. Binding of C4BP to S. pneumoniae is a known virulence mechanism of this pathogen and it was increased in the presence of plasminogen. Interestingly, the acute phase variant of C4BP lacking the β-chain and protein S binds plasminogen much stronger than the main isoform containing the β-chain and protein S. Indeed, the complement control protein (CCP) 8 domain of C4BP, which would otherwise be sterically hindered by the β-chain, primarily mediates this interaction. Moreover, the lysine-binding sites in plasminogen kringle domains facilitate the C4BP-plasminogen interaction. Furthermore, C4BP readily forms complexes with plasminogen in fluid phase and such complexes are present in human serum and plasma. Importantly, while the presence of plasminogen did not affect the factor I cofactor activity of C4BP, the activation of plasminogen by urokinase-type plasminogen activator to active plasmin was significantly augmented in the presence of C4BP. Taken together, our data demonstrate a novel interaction between two proteins of the complement and fibrinolytic system. Most complexes might be formed during the acute phase of inflammation and have an effect on the homeostasis at the site of injury or acute inflammation.}},
author = {{Agarwal, Vaibhav and Talens, Simone and Grandits, Alexander M and Blom, Anna}},
issn = {{1083-351X}},
language = {{eng}},
number = {{30}},
pages = {{18333--18342}},
publisher = {{American Society for Biochemistry and Molecular Biology}},
series = {{Journal of Biological Chemistry}},
title = {{A novel interaction between complement inhibitor C4b-binding protein and plasminogen that enhances plasminogen activation.}},
url = {{http://dx.doi.org/10.1074/jbc.M114.619494}},
doi = {{10.1074/jbc.M114.619494}},
volume = {{290}},
year = {{2015}},
}