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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)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Biological Chemistry
volume
281
issue
6
pages
3690 - 3697
publisher
ASBMB
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
2007-10-05 14:38:58
date last changed
2019-07-28 03:23:47
@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    = {ASBMB},
  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},
  volume       = {281},
  year         = {2006},
}