ArticlePLoS pathogens2006
Extreme sequence divergence but conserved ligand-binding specificity in Streptococcus pyogenes M protein.
Article in PLoS pathogens, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 65 citations in OpenAlex.
- Binding of complement inhibitor C4b-binding protein to a highly virulent Streptococcus pyogenes M1 strain is mediated by protein H and enhances adhesion to and invasion of endothelial cells.The Journal of biological chemistry · 2013Trial
- Penicillin-Binding Proteins inAntibiotics (Basel, Switzerland) · 2026Review
- Conservation of C4BP-binding sequence patterns in Streptococcus pyogenes M and Enn proteins.The Journal of biological chemistry · 2024Article
- The germ theory revisited: A noncentric view on infection outcome.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- C4b-Binding Protein and Factor H Attenuate NLRP3 Inflammasome-Mediated Signalling Response during Group A Streptococci Infection in Human Cells.Journal of innate immunity · 2024Article
- Defining A Global Map of Functional Group-based 3D Ligand-binding Motifs.Genomics, proteomics & bioinformatics · 2022Article
- Streptococcus pyogenes Forms Serotype- and Local Environment-Dependent Interspecies Protein Complexes.mSystems · 2021Article
- Subdominance in Antibody Responses: Implications for Vaccine Development.Microbiology and molecular biology reviews : MMBR · 2020Review
- Complement Evasion Strategies of Human Pathogenic Bacteria.Indian journal of microbiology · 2020Review
- Novel structure of the N-terminal helical domain of BibA, a group B streptococcus immunogenic bacterial adhesin.Acta crystallographica. Section D, Structural biology · 2020Article
- Molecular Epidemiology, Ecology, and Evolution of Group A Streptococci.Microbiology spectrum · 2018Review
- Human IgG Increases Virulence ofJournal of immunology (Baltimore, Md. : 1950) · 2018Article
- Variation, Indispensability, and Masking in the M protein.Trends in microbiology · 2018Review
- Structure-based design of broadly protective group a streptococcal M protein-based vaccines.Vaccine · 2017Article
- Antigenic Variation and Immune Escape in the MTBC.Advances in experimental medicine and biology · 2017Review
- Structural biology: Variability without change.Nature microbiology · 2016Article
- Conserved patterns hidden within group A Streptococcus M protein hypervariability recognize human C4b-binding protein.Nature microbiology · 2016Article
- Sequence variability is correlated with weak immunogenicity in Streptococcus pyogenes M protein.MicrobiologyOpen · 2015Article
- Virulence of Group A Streptococci Is Enhanced by Human Complement Inhibitors.PLoS pathogens · 2015Article
- Molecular epidemiology and genomics of group A Streptococcus.Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases · 2015Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Many pathogenic microorganisms evade host immunity through extensive sequence variability in a protein region targeted by protective antibodies. In spite of the sequence variability, a variable region commonly retains an important ligand-binding function, reflected in the presence of a highly conserved sequence motif. Here, we analyze the limits of sequence divergence in a ligand-binding region by characterizing the hypervariable region (HVR) of Streptococcus pyogenes M protein. Our studies were focused on HVRs that bind the human complement regulator C4b-binding protein (C4BP), a ligand that confers phagocytosis resistance. A previous comparison of C4BP-binding HVRs identified residue identities that could be part of a binding motif, but the extended analysis reported here shows that no residue identities remain when additional C4BP-binding HVRs are included. Characterization of the HVR in the M22 protein indicated that two relatively conserved Leu residues are essential for C4BP binding, but these residues are probably core residues in a coiled-coil, implying that they do not directly contribute to binding. In contrast, substitution of either of two relatively conserved Glu residues, predicted to be solvent-exposed, had no effect on C4BP binding, although each of these changes had a major effect on the antigenic properties of the HVR. Together, these findings show that HVRs of M proteins have an extraordinary capacity for sequence divergence and antigenic variability while retaining a specific ligand-binding function.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.