This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Blackmore, T. K.
Right arrow Articles by Gordon, D. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Blackmore, T. K.
Right arrow Articles by Gordon, D. L.

 Previous Article  |  Next Article 

Infect Immun, April 1998, p. 1427-1431, Vol. 66, No. 4
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

M Protein of the Group A Streptococcus Binds to the Seventh Short Consensus Repeat of Human Complement Factor H

Timothy K. Blackmore,1,* Vincent A. Fischetti,2 Tania A. Sadlon,1 Helena M. Ward,1 and David L. Gordon1

Department of Microbiology and Infectious Diseases, Flinders University of South Australia and Flinders Medical Centre, Bedford Park, South Australia 5042, Australia,1 and Laboratory of Bacterial Pathogenesis and Immunology, The Rockefeller University, New York, New York 100212

Received 25 September 1997/Returned for modification 30 October 1997/Accepted 8 January 1998

Streptococcus pyogenes evades complement by binding the complement-regulatory protein factor H (fH) via the central conserved C-repeat region of M protein. However, the corresponding binding region within fH has not previously been precisely localized. fH is composed of 20 conserved modules called short consensus repeats (SCRs), each of which contains approximately 60 amino acids. A series of fH truncated and deletion mutants were prepared, and their interaction with M6 protein was examined. The M protein binding site was initially localized to SCRs 6 to 15 as demonstrated by ligand dot blotting, chemical cross-linking, and enzyme-linked immunosorbent assay. SCR 7 was then shown to contain the M protein binding site, as a construct consisting of the first seven SCRs bound M protein but a construct containing the first six SCRs did not bind. In addition, deletion of SCR 7 from full-length fH abolished binding to M protein. SCR 7 is known to contain a heparin binding domain, and binding of fH to M6 protein was almost totally inhibited in the presence of 400 U of heparin per ml. These results localize the M6 protein binding site of fH to SCR 7 and indicate that it is in close proximity to the heparin binding site.

* Corresponding author. Mailing address: Department of Microbiology and Infectious Diseases, Flinders Medical Centre, Bedford Park, South Australia 5042, Australia. Phone: (61-8)-8204-4720. Fax: (61-8)-8276-8656. E-mail: Tim.Blackmore{at}flinders.edu.au.




This article has been cited by other articles:

  • Ormsby, R. J., Ranganathan, S., Tong, J. C., Griggs, K. M., Dimasi, D. P., Hewitt, A. W., Burdon, K. P., Craig, J. E., Hoh, J., Gordon, D. L. (2008). Functional and Structural Implications of the Complement Factor H Y402H Polymorphism Associated with Age-Related Macular Degeneration. IOVS 49: 1763-1770 [Abstract] [Full Text]  
  • Herzberger, P., Siegel, C., Skerka, C., Fingerle, V., Schulte-Spechtel, U., van Dam, A., Wilske, B., Brade, V., Zipfel, P. F., Wallich, R., Kraiczy, P. (2007). Human Pathogenic Borrelia spielmanii sp. nov. Resists Complement-Mediated Killing by Direct Binding of Immune Regulators Factor H and Factor H-Like Protein 1. Infect. Immun. 75: 4817-4825 [Abstract] [Full Text]  
  • Baird, P. N., Islam, F. M. A., Richardson, A. J., Cain, M., Hunt, N., Guymer, R. (2006). Analysis of the Y402H Variant of the Complement Factor H Gene in Age-Related Macular Degeneration.. IOVS 47: 4194-4198 [Abstract] [Full Text]  
  • Lu, L., Ma, Y., Zhang, J.-R. (2006). Streptococcus pneumoniae Recruits Complement Factor H through the Amino Terminus of CbpA. J. Biol. Chem. 281: 15464-15474 [Abstract] [Full Text]  
  • Nagano, N., Nagano, Y., Nakano, R., Okamoto, R., Inoue, M. (2006). Genetic diversity of the C protein beta-antigen gene and its upstream regions within clonally related groups of type Ia and Ib group B streptococci.. Microbiology 152: 771-778 [Abstract] [Full Text]  
  • McRae, J. L., Duthy, T. G., Griggs, K. M., Ormsby, R. J., Cowan, P. J., Cromer, B. A., McKinstry, W. J., Parker, M. W., Murphy, B. F., Gordon, D. L. (2005). Human Factor H-Related Protein 5 Has Cofactor Activity, Inhibits C3 Convertase Activity, Binds Heparin and C-Reactive Protein, and Associates with Lipoprotein. J. Immunol. 174: 6250-6256 [Abstract] [Full Text]  
  • Haines, J. L., Hauser, M. A., Schmidt, S., Scott, W. K., Olson, L. M., Gallins, P., Spencer, K. L., Kwan, S. Y., Noureddine, M., Gilbert, J. R., Schnetz-Boutaud, N., Agarwal, A., Postel, E. A., Pericak-Vance, M. A. (2005). Complement Factor H Variant Increases the Risk of Age-Related Macular Degeneration. Science 308: 419-421 [Abstract] [Full Text]  
  • Biedzka-Sarek, M., Venho, R., Skurnik, M. (2005). Role of YadA, Ail, and Lipopolysaccharide in Serum Resistance of Yersinia enterocolitica Serotype O:3. Infect. Immun. 73: 2232-2244 [Abstract] [Full Text]  
  • Kimura, Y., Inoue, N., Fukui, A., Oshiumi, H., Matsumoto, M., Nonaka, M., Kuratani, S., Fujita, T., Nonaka, M., Seya, T. (2004). A Short Consensus Repeat-Containing Complement Regulatory Protein of Lamprey That Participates in Cleavage of Lamprey Complement 3. J. Immunol. 173: 1118-1128 [Abstract] [Full Text]  
  • Dave, S., Carmicle, S., Hammerschmidt, S., Pangburn, M. K., McDaniel, L. S. (2004). Dual Roles of PspC, a Surface Protein of Streptococcus pneumoniae, in Binding Human Secretory IgA and Factor H. J. Immunol. 173: 471-477 [Abstract] [Full Text]  
  • Jarva, H., Hellwage, J., Jokiranta, T. S., Lehtinen, M. J., Zipfel, P. F., Meri, S. (2004). The Group B Streptococcal {beta} and Pneumococcal Hic Proteins Are Structurally Related Immune Evasion Molecules That Bind the Complement Inhibitor Factor H in an Analogous Fashion. J. Immunol. 172: 3111-3118 [Abstract] [Full Text]  
  • Kraiczy, P., Hellwage, J., Skerka, C., Becker, H., Kirschfink, M., Simon, M. M., Brade, V., Zipfel, P. F., Wallich, R. (2004). Complement Resistance of Borrelia burgdorferi Correlates with the Expression of BbCRASP-1, a Novel Linear Plasmid-encoded Surface Protein That Interacts with Human Factor H and FHL-1 and Is Unrelated to Erp Proteins. J. Biol. Chem. 279: 2421-2429 [Abstract] [Full Text]  
  • Pandiripally, V., Wei, L., Skerka, C., Zipfel, P. F., Cue, D. (2003). Recruitment of Complement Factor H-Like Protein 1 Promotes Intracellular Invasion by Group A Streptococci. Infect. Immun. 71: 7119-7128 [Abstract] [Full Text]  
  • Pangburn, M. K. (2002). Cutting Edge: Localization of the Host Recognition Functions of Complement Factor H at the Carboxyl-Terminal: Implications for Hemolytic Uremic Syndrome. J. Immunol. 169: 4702-4706 [Abstract] [Full Text]  
  • Duthy, T. G., Ormsby, R. J., Giannakis, E., Ogunniyi, A. D., Stroeher, U. H., Paton, J. C., Gordon, D. L. (2002). The Human Complement Regulator Factor H Binds Pneumococcal Surface Protein PspC via Short Consensus Repeats 13 to 15. Infect. Immun. 70: 5604-5611 [Abstract] [Full Text]  
  • Giannakis, E., Jokiranta, T. S., Ormsby, R. J., Duthy, T. G., Male, D. A., Christiansen, D., Fischetti, V. A., Bagley, C., Loveland, B. E., Gordon, D. L. (2002). Identification of the Streptococcal M Protein Binding Site on Membrane Cofactor Protein (CD46). J. Immunol. 168: 4585-4592 [Abstract] [Full Text]  
  • Areschoug, T., Stalhammar-Carlemalm, M., Karlsson, I., Lindahl, G. (2002). Streptococcal beta Protein Has Separate Binding Sites for Human Factor H and IgA-Fc. J. Biol. Chem. 277: 12642-12648 [Abstract] [Full Text]  
  • Jarva, H., Janulczyk, R., Hellwage, J., Zipfel, P. F., Bjorck, L., Meri, S. (2002). Streptococcus pneumoniae Evades Complement Attack and Opsonophagocytosis by Expressing the pspC Locus-Encoded Hic Protein That Binds to Short Consensus Repeats 8-11 of Factor H. J. Immunol. 168: 1886-1894 [Abstract] [Full Text]  
  • Jarva, H., Jokiranta, T. S., Hellwage, J., Zipfel, P. F., Meri, S. (1999). Regulation of Complement Activation by C-Reactive Protein: Targeting the Complement Inhibitory Activity of Factor H by an Interaction with Short Consensus Repeat Domains 7 and 8-11. J. Immunol. 163: 3957-3962 [Abstract] [Full Text]  
  • Navarre, W. W., Schneewind, O. (1999). Surface Proteins of Gram-Positive Bacteria and Mechanisms of Their Targeting to the Cell Wall Envelope. Microbiol. Mol. Biol. Rev. 63: 174-229 [Abstract] [Full Text]  
  • Johnsson, E., Berggard, K., Kotarsky, H., Hellwage, J., Zipfel, P. F., Sjobring, U., Lindahl, G. (1998). Role of the Hypervariable Region in Streptococcal M Proteins: Binding of a Human Complement Inhibitor. J. Immunol. 161: 4894-4901 [Abstract] [Full Text]  
  • Fedarko, N. S., Fohr, B., Robey, P. G., Young, M. F., Fisher, L. W. (2000). Factor H Binding to Bone Sialoprotein and Osteopontin Enables Tumor Cell Evasion of Complement-mediated Attack. J. Biol. Chem. 275: 16666-16672 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»