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• W2133807005 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." @default.
• W2133807005 created "2016-06-24" @default.
• W2133807005 creator A5061837492 @default.
• W2133807005 creator A5070625264 @default.
• W2133807005 creator A5071279105 @default.
• W2133807005 creator A5077978546 @default.
• W2133807005 date "2006-05-26" @default.
• W2133807005 modified "2023-10-16" @default.
• W2133807005 title "Extreme Sequence Divergence but Conserved Ligand-Binding Specificity in Streptococcus pyogenes M Protein" @default.
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• W2133807005 doi "https://doi.org/10.1371/journal.ppat.0020047" @default.
• W2133807005 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/1464397" @default.
• W2133807005 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/16733543" @default.
• W2133807005 hasPublicationYear "2006" @default.
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