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Protein GRAB of streptococcus pyogenes regulates proteolysis at the bacterial surface by binding alpha2-macroglobulin

Rasmussen, Magnus LU ; Muller, H P and Björck, Lars LU (1999) In Journal of Biological Chemistry 274(22). p.15336-15344
Abstract
In the molecular interplay between pathogenic microorganisms and their host, proteolytic mechanisms are believed to play a crucial role. Here we find that the important human pathogen Streptococcus pyogenes (group A Streptococcus) expresses a surface protein with high affinity (Ka = 2.0 x 10(8) M-1) for alpha2-macroglobulin (alpha2M), the dominating proteinase inhibitor of human plasma. The immunoglobulin-binding protein G of group C and G streptococci also contains an alpha2M-binding domain and a gene encoding protein GRAB (protein G-related alpha2M-binding protein) was identified in the S. pyogenes Genome Sequencing data base. The grab gene is present in most S. pyogenes strains and is well conserved. Protein GRAB has typical features of... (More)
In the molecular interplay between pathogenic microorganisms and their host, proteolytic mechanisms are believed to play a crucial role. Here we find that the important human pathogen Streptococcus pyogenes (group A Streptococcus) expresses a surface protein with high affinity (Ka = 2.0 x 10(8) M-1) for alpha2-macroglobulin (alpha2M), the dominating proteinase inhibitor of human plasma. The immunoglobulin-binding protein G of group C and G streptococci also contains an alpha2M-binding domain and a gene encoding protein GRAB (protein G-related alpha2M-binding protein) was identified in the S. pyogenes Genome Sequencing data base. The grab gene is present in most S. pyogenes strains and is well conserved. Protein GRAB has typical features of a surface-attached protein of Gram-positive bacteria. It also contains a region homologous to parts of the alpha2M-binding domain of protein G and a variable number of a unique 28-amino acid-long repeat. Using Escherichia coli-produced protein GRAB and synthetic GRAB peptides, the alpha2M-binding region was mapped to the NH2-terminal part of protein GRAB, which is the region with homology to protein G. An isogenic S. pyogenes mutant lacking surface-associated protein GRAB showed no alpha2M binding activity and was attenuated in virulence when injected intraperitoneally in mice. Finally, alpha2M bound to the bacterial surface via protein GRAB was found to entrap and inhibit the activity of both S. pyogenes and host proteinases, thereby protecting important virulence determinants from proteolytic degradation. This regulation of proteolytic activity at the bacterial surface should affect the host-microbe relation during S. pyogenes infections. (Less)
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author
organization
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Contribution to journal
publication status
published
subject
in
Journal of Biological Chemistry
volume
274
issue
22
pages
15336 - 15344
publisher
ASBMB
external identifiers
  • pmid:10336419
ISSN
1083-351X
language
English
LU publication?
yes
id
657c53e7-18e2-4509-8daa-1a631306ecc2 (old id 1115780)
alternative location
http://www.jbc.org/cgi/content/full/274/22/15336
date added to LUP
2008-07-08 13:58:32
date last changed
2016-04-15 20:08:34
@article{657c53e7-18e2-4509-8daa-1a631306ecc2,
  abstract     = {In the molecular interplay between pathogenic microorganisms and their host, proteolytic mechanisms are believed to play a crucial role. Here we find that the important human pathogen Streptococcus pyogenes (group A Streptococcus) expresses a surface protein with high affinity (Ka = 2.0 x 10(8) M-1) for alpha2-macroglobulin (alpha2M), the dominating proteinase inhibitor of human plasma. The immunoglobulin-binding protein G of group C and G streptococci also contains an alpha2M-binding domain and a gene encoding protein GRAB (protein G-related alpha2M-binding protein) was identified in the S. pyogenes Genome Sequencing data base. The grab gene is present in most S. pyogenes strains and is well conserved. Protein GRAB has typical features of a surface-attached protein of Gram-positive bacteria. It also contains a region homologous to parts of the alpha2M-binding domain of protein G and a variable number of a unique 28-amino acid-long repeat. Using Escherichia coli-produced protein GRAB and synthetic GRAB peptides, the alpha2M-binding region was mapped to the NH2-terminal part of protein GRAB, which is the region with homology to protein G. An isogenic S. pyogenes mutant lacking surface-associated protein GRAB showed no alpha2M binding activity and was attenuated in virulence when injected intraperitoneally in mice. Finally, alpha2M bound to the bacterial surface via protein GRAB was found to entrap and inhibit the activity of both S. pyogenes and host proteinases, thereby protecting important virulence determinants from proteolytic degradation. This regulation of proteolytic activity at the bacterial surface should affect the host-microbe relation during S. pyogenes infections.},
  author       = {Rasmussen, Magnus and Muller, H P and Björck, Lars},
  issn         = {1083-351X},
  language     = {eng},
  number       = {22},
  pages        = {15336--15344},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {Protein GRAB of streptococcus pyogenes regulates proteolysis at the bacterial surface by binding alpha2-macroglobulin},
  volume       = {274},
  year         = {1999},
}