M protein of the group A streptococcus binds to the seventh short consensus repeat of human complement factor H

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dc.contributor.authorBlackmore, T.
dc.contributor.authorFischetti, V.
dc.contributor.authorSadlon, T.
dc.contributor.authorWard, H.
dc.contributor.authorGordon, D.
dc.date.issued1998
dc.description.abstractStreptococcus 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.
dc.description.statementofresponsibilityTimothy K. Blackmore, Vincent A. Fischetti, Tania A. Sadlon, Helena M. Ward, and David L. Gordon
dc.identifier.citationInfection and Immunity, 1998; 66(4):1427-1431
dc.identifier.doi10.1128/iai.66.4.1427-1431.1998
dc.identifier.issn0019-9567
dc.identifier.issn1098-5522
dc.identifier.orcidWard, H. [0000-0002-3831-1205]
dc.identifier.urihttp://hdl.handle.net/2440/81791
dc.language.isoen
dc.publisherAmerican Society for Microbiology
dc.rightsCopyright © 1998 American Society for Microbiology
dc.source.urihttp://iai.asm.org/content/66/4/1427.abstract
dc.subjectCHO Cells
dc.subjectAnimals
dc.subjectHumans
dc.subjectStreptococcus pyogenes
dc.subjectHeparin
dc.subjectBacterial Proteins
dc.subjectBacterial Outer Membrane Proteins
dc.subjectComplement Factor H
dc.subjectCarrier Proteins
dc.subjectAntigens, Bacterial
dc.subjectBinding Sites
dc.subjectCricetinae
dc.titleM protein of the group A streptococcus binds to the seventh short consensus repeat of human complement factor H
dc.typeJournal article
pubs.publication-statusPublished

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