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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.




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