Human C4b-binding protein, structural basis for interaction with streptococcal M protein, a major bacterial virulence factor
Jenkins, HT ; Mark, Linda LU ; Ball, G ; Persson, Jenny LU ; Lindahl, Gunnar LU ; Uhrin, D ; Blom, Anna LU
and Barlow, PN
(2006)
In Journal of Biological Chemistry
281(6).
p.3690-3697
- Abstract
- Human C4b-binding protein (C4BP) protects host tissue, and those pathogens able to hijack this plasma glycoprotein, from complement-mediated destruction. We now show that the first two complement control protein (CCP) modules of the C4BP alpha-chain, plus the four residues connecting them, are necessary and sufficient for binding a bacterial virulence factor, the Streptococcus pyogenes M4 (Arp4) protein. Structure determination by NMR reveals two tightly coupled CCP modules in an elongated arrangement within this region of C4BP. Chemical shift perturbation studies demonstrate that the N-terminal, hypervariable region of M4 binds to a site including strand 1 of CCP module 2. This interaction is accompanied by an intermodular reorientation... (More)
- Human C4b-binding protein (C4BP) protects host tissue, and those pathogens able to hijack this plasma glycoprotein, from complement-mediated destruction. We now show that the first two complement control protein (CCP) modules of the C4BP alpha-chain, plus the four residues connecting them, are necessary and sufficient for binding a bacterial virulence factor, the Streptococcus pyogenes M4 (Arp4) protein. Structure determination by NMR reveals two tightly coupled CCP modules in an elongated arrangement within this region of C4BP. Chemical shift perturbation studies demonstrate that the N-terminal, hypervariable region of M4 binds to a site including strand 1 of CCP module 2. This interaction is accompanied by an intermodular reorientation within C4BP. We thus provide a detailed picture of an interaction whereby a pathogen evades complement. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/417800
- author
- Jenkins, HT
; Mark, Linda
LU
; Ball, G
; Persson, Jenny
LU
; Lindahl, Gunnar
LU
; Uhrin, D
; Blom, Anna
LU
and Barlow, PN
- organization
- publishing date
- 2006
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Biological Chemistry
- volume
- 281
- issue
- 6
- pages
- 3690 - 3697
- publisher
- American Society for Biochemistry and Molecular Biology
- external identifiers
-
- pmid:16330538
- wos:000235128200081
- scopus:33645650398
- ISSN
- 1083-351X
- DOI
- 10.1074/jbc.M511563200
- language
- English
- LU publication?
- yes
- id
- acaf46b2-53de-447e-8df2-cc44c9b27b69 (old id 417800)
- date added to LUP
- 2016-04-01 11:55:55
- date last changed
- 2022-03-13 02:39:31
@article{acaf46b2-53de-447e-8df2-cc44c9b27b69,
abstract = {{Human C4b-binding protein (C4BP) protects host tissue, and those pathogens able to hijack this plasma glycoprotein, from complement-mediated destruction. We now show that the first two complement control protein (CCP) modules of the C4BP alpha-chain, plus the four residues connecting them, are necessary and sufficient for binding a bacterial virulence factor, the Streptococcus pyogenes M4 (Arp4) protein. Structure determination by NMR reveals two tightly coupled CCP modules in an elongated arrangement within this region of C4BP. Chemical shift perturbation studies demonstrate that the N-terminal, hypervariable region of M4 binds to a site including strand 1 of CCP module 2. This interaction is accompanied by an intermodular reorientation within C4BP. We thus provide a detailed picture of an interaction whereby a pathogen evades complement.}},
author = {{Jenkins, HT and Mark, Linda and Ball, G and Persson, Jenny and Lindahl, Gunnar and Uhrin, D and Blom, Anna and Barlow, PN}},
issn = {{1083-351X}},
language = {{eng}},
number = {{6}},
pages = {{3690--3697}},
publisher = {{American Society for Biochemistry and Molecular Biology}},
series = {{Journal of Biological Chemistry}},
title = {{Human C4b-binding protein, structural basis for interaction with streptococcal M protein, a major bacterial virulence factor}},
url = {{http://dx.doi.org/10.1074/jbc.M511563200}},
doi = {{10.1074/jbc.M511563200}},
volume = {{281}},
year = {{2006}},
}