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Group G streptococcal IgG binding molecules FOG and protein G have different impacts on opsonization by C1q

Nitsche-Schmitz, D. Patric; Linge, Helena LU ; Sastalla, Inka; Reissmann, Silvana; Frick, Inga-Maria LU and Chhatwal, Gursharan S. (2007) In Journal of Biological Chemistry 282(24). p.17530-17536
Abstract
Recent epidemiological data on diseases caused by beta-hemolytic streptococci belonging to Lancefield group C and G ( GCS, GGS) underline that they are an emerging threat to human health. Among various virulence factors expressed by GCS and GGS isolates from human infections, M and M-like proteins are considered important because of their anti-phagocytic activity. In addition, protein G has been implicated in the accumulation of IgG on the bacterial surface through non-immune binding. The function of this interaction, however, is still unknown. Using isogenic mutants lacking protein G or the M-like protein FOG ( group G streptococci), respectively, we could show that FOG contributes substantially to IgG binding. A detailed characterization... (More)
Recent epidemiological data on diseases caused by beta-hemolytic streptococci belonging to Lancefield group C and G ( GCS, GGS) underline that they are an emerging threat to human health. Among various virulence factors expressed by GCS and GGS isolates from human infections, M and M-like proteins are considered important because of their anti-phagocytic activity. In addition, protein G has been implicated in the accumulation of IgG on the bacterial surface through non-immune binding. The function of this interaction, however, is still unknown. Using isogenic mutants lacking protein G or the M-like protein FOG ( group G streptococci), respectively, we could show that FOG contributes substantially to IgG binding. A detailed characterization of the interaction between IgG and FOG revealed its ability to bind the Fc region of human IgG and its binding to the subclasses IgG1, IgG2, and IgG4. FOG was also found to bind IgG of several animal species. Surface plasmon resonance measurements indicate a high affinity to human IgG with a dissociation constant of 2.4 pM. The binding site was localized in a central motif of FOG. It has long been speculated about anti-opsonic functions of streptococcal Fc-binding proteins. The presented data for the first time provide evidence and, furthermore, indicate functional differences between protein G and FOG. By obstructing the interaction between IgG and C1q, protein G prevented recognition by the classical pathway of the complement system. In contrast, IgG that was bound to FOG remained capable of binding C1q, an effect that may have important consequences in the pathogenesis of GGS infections. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Biological Chemistry
volume
282
issue
24
pages
17530 - 17536
publisher
ASBMB
external identifiers
  • wos:000247084500023
  • scopus:34547113538
ISSN
1083-351X
DOI
10.1074/jbc.M702612200
language
English
LU publication?
yes
id
4cd0ffa9-2be0-4bc7-9967-51bc167d78be (old id 650886)
date added to LUP
2007-12-18 17:35:46
date last changed
2017-11-05 03:31:01
@article{4cd0ffa9-2be0-4bc7-9967-51bc167d78be,
  abstract     = {Recent epidemiological data on diseases caused by beta-hemolytic streptococci belonging to Lancefield group C and G ( GCS, GGS) underline that they are an emerging threat to human health. Among various virulence factors expressed by GCS and GGS isolates from human infections, M and M-like proteins are considered important because of their anti-phagocytic activity. In addition, protein G has been implicated in the accumulation of IgG on the bacterial surface through non-immune binding. The function of this interaction, however, is still unknown. Using isogenic mutants lacking protein G or the M-like protein FOG ( group G streptococci), respectively, we could show that FOG contributes substantially to IgG binding. A detailed characterization of the interaction between IgG and FOG revealed its ability to bind the Fc region of human IgG and its binding to the subclasses IgG1, IgG2, and IgG4. FOG was also found to bind IgG of several animal species. Surface plasmon resonance measurements indicate a high affinity to human IgG with a dissociation constant of 2.4 pM. The binding site was localized in a central motif of FOG. It has long been speculated about anti-opsonic functions of streptococcal Fc-binding proteins. The presented data for the first time provide evidence and, furthermore, indicate functional differences between protein G and FOG. By obstructing the interaction between IgG and C1q, protein G prevented recognition by the classical pathway of the complement system. In contrast, IgG that was bound to FOG remained capable of binding C1q, an effect that may have important consequences in the pathogenesis of GGS infections.},
  author       = {Nitsche-Schmitz, D. Patric and Linge, Helena and Sastalla, Inka and Reissmann, Silvana and Frick, Inga-Maria and Chhatwal, Gursharan S.},
  issn         = {1083-351X},
  language     = {eng},
  number       = {24},
  pages        = {17530--17536},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {Group G streptococcal IgG binding molecules FOG and protein G have different impacts on opsonization by C1q},
  url          = {http://dx.doi.org/10.1074/jbc.M702612200},
  volume       = {282},
  year         = {2007},
}