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Infect Immun, April 1998, p. 1427-1431, Vol. 66, No. 4
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.
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
*
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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