Divergence in the plasminogen-binding group A streptococcal M protein family : Functional conservation of binding site and potential role for immune selection of variants

Sanderson-Smith, Martina, Batzloff, Michael, Sriprakash, Kabada S., Dowton, Mark, Ranson, Marie and Walker, Mark J. (2006) Divergence in the plasminogen-binding group A streptococcal M protein family : Functional conservation of binding site and potential role for immune selection of variants. Journal of Biological Chemistry, 281 6: 3217-3226. doi:10.1074/jbc.M508758200

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Author Sanderson-Smith, Martina
Batzloff, Michael
Sriprakash, Kabada S.
Dowton, Mark
Ranson, Marie
Walker, Mark J.
Title Divergence in the plasminogen-binding group A streptococcal M protein family : Functional conservation of binding site and potential role for immune selection of variants
Journal name Journal of Biological Chemistry   Check publisher's open access policy
ISSN 0021-9258
Publication date 2006-02
Sub-type Article (original research)
DOI 10.1074/jbc.M508758200
Open Access Status File (Publisher version)
Volume 281
Issue 6
Start page 3217
End page 3226
Total pages 10
Place of publication Bethesda, MD, United States
Publisher American society for Biochemistry and Molecular Biology
Language eng
Formatted abstract
Group A streptococci (GAS) display receptors for the human zymogen plasminogen on the cell surface, one of which is the plasminogen-binding group A streptococcal M protein (PAM). Characterization of PAM genes from 12 GAS isolates showed significant variation within the plasminogen-binding repeat motifs (a1/a2) of this protein. To determine the impact of sequence variation on protein function, recombinant proteins representing five naturally occurring variants of PAM, together with a recombinant M1 protein, were expressed and purified. Equilibrium dissociation constants for the interaction of PAM variants with biotinylated Glu-plasminogen ranged from 1.58 to 4.99 nM. Effective concentrations of prototype PAM required for 50% inhibition of plasminogen binding to immobilized PAM variants ranged from 0.68 to 22.06 nM. These results suggest that although variation in the a1/a2 region of the PAM protein does affect the comparative affinity of PAM variants, the functional capacity to bind plasminogen is conserved. Additionally, a potential role for the a1 region of PAM in eliciting a protective immune response was investigated by using a mouse model for GAS infection. The a1 region of PAM was found to protect immunized mice challenged with a PAM-positive GAS strain. These data suggest a link between selective immune pressure against the plasminogen-binding repeats and the functional conservation of the binding domain in PAM variants. © 2006 by The American Society for Biochemistry and Molecular Biology, Inc.
Keyword Population Genetic-Structure
Bacterial Surface Protein
Escherichia-Coli
Kringle-2 Domain
Alpha-Enolase
Pyogenes
Pam
Evolution
Region
Streptokinase
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collections: ERA 2012 Admin Only
School of Chemistry and Molecular Biosciences
 
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