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dc.contributor.authorGiannakis, E
dc.contributor.authorJokiranta, TS
dc.contributor.authorOrmsby, RJ
dc.contributor.authorDuthy, TG
dc.contributor.authorMale, DA
dc.contributor.authorChristiansen, D
dc.contributor.authorFischetti, VA
dc.contributor.authorBagley, C
dc.contributor.authorLoveland, BE
dc.contributor.authorGordon, DL
dc.date.available2014-05-21T19:24:49Z
dc.date.issued2002-05-01
dc.identifierhttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000175263000044&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=d4d813f4571fa7d6246bdc0dfeca3a1c
dc.identifier.citationGiannakis, 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). JOURNAL OF IMMUNOLOGY, 168 (9), pp.4585-4592. https://doi.org/10.4049/jimmunol.168.9.4585.
dc.identifier.issn0022-1767
dc.identifier.urihttp://hdl.handle.net/11343/26246
dc.descriptionC1 - Journal Articles Refereed
dc.description.abstractAdherence of group A streptococcus (GAS) to keratinocytes is mediated by an interaction between human CD46 (membrane cofactor protein) with streptococcal cell surface M protein. CD46 belongs to a family of proteins that contain structurally related short consensus repeat (SCR) domains and regulate the activation of the complement components C3b and/or C4b. CD46 possesses four SCR domains and the aim of this study was to characterize their interaction with M protein. Following confirmation of the M6 protein-dependent interaction between GAS and human keratinocytes, we demonstrated that M6 protein binds soluble recombinant CD46 protein and to a CD46 construct containing only SCRs 3 and 4. M6 protein did not bind to soluble recombinant CD46 chimeric proteins that had the third and/or fourth SCR domains replaced with the corresponding domains from another complement regulator, CD55 (decay-accelerating factor). Homology-based molecular modeling of CD46 SCRs 3 and 4 revealed a cluster of positively charged residues between the interface of these SCR domains similar to the verified M protein binding sites on the plasma complement regulators factor H and C4b-binding protein. The presence of excess M6 protein did not inhibit the cofactor activity of CD46 and the presence of excess C3b did not inhibit the ability of CD46 to bind M6 protein by ELISA. In conclusion, 1) adherence of M6 GAS to keratinocytes is M protein dependent and 2) a major M protein binding site is located within SCRs 3 and 4, probably at the interface of these two domains, at a site distinct from the C3b-binding and cofactor site of CD46.
dc.formatapplication/pdf
dc.languageEnglish
dc.publisherAMER ASSOC IMMUNOLOGISTS
dc.subjectImmunology not elsewhere classified; Immune System and Allergy
dc.titleIdentification of the streptococcal M protein binding site on membrane cofactor protein (CD46)
dc.typeJournal Article
dc.identifier.doi10.4049/jimmunol.168.9.4585
melbourne.peerreviewPeer Reviewed
melbourne.affiliationThe University of Melbourne
melbourne.affiliation.departmentPathology
melbourne.source.titleJOURNAL OF IMMUNOLOGY
melbourne.source.volume168
melbourne.source.issue9
melbourne.source.pages4585-4592
dc.research.coderfcd320299
dc.research.codeseo1998730102
melbourne.publicationid10988
melbourne.elementsid253386
melbourne.contributor.authorChristiansen, Dale
melbourne.contributor.authorLOVELAND, BRUCE
dc.identifier.eissn1550-6606
melbourne.accessrightsThis item is currently not available from this repository


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