2.50
Hdl Handle:
http://hdl.handle.net/10033/65054
Title:
Crucial role of the CB3-region of collagen IV in PARF-induced acute rheumatic fever.
Authors:
Dinkla, Katrin; Talay, Susanne R; Mörgelin, Matthias; Graham, Rikki M A; Rohde, Manfred ( 0000-0003-0522-3580 ) ; Nitsche-Schmitz, D Patric; Chhatwal, Gursharan S
Abstract:
Acute rheumatic fever (ARF) and rheumatic heart disease are serious autoimmune sequelae to infections with Streptococcus pyogenes. Streptococcal M-proteins have been implicated in ARF pathogenesis. Their interaction with collagen type IV (CIV) is a triggering step that induces generation of collagen-specific auto-antibodies. Electron microscopy of the protein complex between M-protein type 3 (M3-protein) and CIV identified two prominent binding sites of which one is situated in the CB3-region of CIV. In a radioactive binding assay, M3-protein expressing S. pyogenes and S. gordonii bound the CB3-fragment. Detailed analysis of the interactions by surface plasmon resonance measurements and site directed mutagenesis revealed high affinity interactions with dissociation constants in the nanomolar range that depend on the recently described collagen binding motif of streptococcal M-proteins. Because of its role in the induction of disease-related collagen autoimmunity the motif is referred to as "peptide associated with rheumatic fever" (PARF). Both, sera of mice immunized with M3-protein as well as sera from patients with ARF contained anti-CB3 auto-antibodies, indicating their contribution to ARF pathogenesis. The identification of the CB3-region as a binding partner for PARF directs the further approaches to understand the unusual autoimmune pathogenesis of PARF-dependent ARF and forms a molecular basis for a diagnostic test that detects rheumatogenic streptococci.
Affiliation:
Department of Microbial Pathogenesis, Helmholtz Centre for Infection Research, Braunschweig, Germany.
Citation:
Crucial role of the CB3-region of collagen IV in PARF-induced acute rheumatic fever. 2009, 4 (3):e4666 PLoS ONE
Journal:
PLoS ONE
Issue Date:
2009
URI:
http://hdl.handle.net/10033/65054
DOI:
10.1371/journal.pone.0004666
PubMed ID:
19252743
Additional Links:
http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=19252743
Type:
Article
Language:
en
ISSN:
1932-6203
Appears in Collections:
Publications of Dept. Medizinische Mikrobiologie (MMIK)

Full metadata record

DC FieldValue Language
dc.contributor.authorDinkla, Katrinen
dc.contributor.authorTalay, Susanne Ren
dc.contributor.authorMörgelin, Matthiasen
dc.contributor.authorGraham, Rikki M Aen
dc.contributor.authorRohde, Manfreden
dc.contributor.authorNitsche-Schmitz, D Patricen
dc.contributor.authorChhatwal, Gursharan Sen
dc.date.accessioned2009-04-16T10:35:51Zen
dc.date.available2009-04-16T10:35:51Zen
dc.date.issued2009en
dc.identifier.citationCrucial role of the CB3-region of collagen IV in PARF-induced acute rheumatic fever. 2009, 4 (3):e4666 PLoS ONEen
dc.identifier.issn1932-6203en
dc.identifier.pmid19252743en
dc.identifier.doi10.1371/journal.pone.0004666en
dc.identifier.urihttp://hdl.handle.net/10033/65054en
dc.description.abstractAcute rheumatic fever (ARF) and rheumatic heart disease are serious autoimmune sequelae to infections with Streptococcus pyogenes. Streptococcal M-proteins have been implicated in ARF pathogenesis. Their interaction with collagen type IV (CIV) is a triggering step that induces generation of collagen-specific auto-antibodies. Electron microscopy of the protein complex between M-protein type 3 (M3-protein) and CIV identified two prominent binding sites of which one is situated in the CB3-region of CIV. In a radioactive binding assay, M3-protein expressing S. pyogenes and S. gordonii bound the CB3-fragment. Detailed analysis of the interactions by surface plasmon resonance measurements and site directed mutagenesis revealed high affinity interactions with dissociation constants in the nanomolar range that depend on the recently described collagen binding motif of streptococcal M-proteins. Because of its role in the induction of disease-related collagen autoimmunity the motif is referred to as "peptide associated with rheumatic fever" (PARF). Both, sera of mice immunized with M3-protein as well as sera from patients with ARF contained anti-CB3 auto-antibodies, indicating their contribution to ARF pathogenesis. The identification of the CB3-region as a binding partner for PARF directs the further approaches to understand the unusual autoimmune pathogenesis of PARF-dependent ARF and forms a molecular basis for a diagnostic test that detects rheumatogenic streptococci.en
dc.language.isoenen
dc.relation.urlhttp://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=19252743en
dc.titleCrucial role of the CB3-region of collagen IV in PARF-induced acute rheumatic fever.en
dc.typeArticleen
dc.contributor.departmentDepartment of Microbial Pathogenesis, Helmholtz Centre for Infection Research, Braunschweig, Germany.en
dc.identifier.journalPLoS ONEen

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