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Conformational characteristics of the complete sequence of group A streptococcal M6 protein
V A Fischetti1, D A Parry, B L Trus
1Rockefeller University, New York, New York 10021.
Abstract:
M protein is considered a virulence determinant on the streptococcal cell wall by virtue of its ability to allow the organism to resist attack by human neutrophils. The complete DNA sequence of the M6 gene from streptococcal strain D471 has allowed, for the first time, the study of the structural characteristics of the amino acid sequence of an entire M protein molecule. Predictive secondary structural analysis revealed that the majority of this fibrillar molecule exhibits strong alpha-helical potential and that, except for the ends, nonpolar residues in the central region of the molecule exhibit the 7-residue periodicity typical for coiled-coil proteins. Differences in this heptad pattern of nonpolar residues allow this central rod region to be divided into three subdomains which correlate essentially with the repeat regions A, B, and C/D in the M6 protein sequence. Alignment of the N-terminal half of the M6 sequence with PepM5, the N-terminal half of the M5 protein, revealed that 42% of the amino acids were identical. The majority of the identities were "core" nonpolar residues of the heptad periodicity which are necessary for the maintenance of the coiled coil. Thus, conservation of structure in a sequence-variable region of these molecules may be biologically significant. Results suggest that serologically different M proteins may be built according to a basic scheme: an extended central coiled-coil rod domain (which may vary in size among strains) flanked by functional end domains.
Insights
Streptococcal M protein
Area of Science:
- Microbiology
- Structural Biology
- Genetics
Background:
- M protein is a streptococcal virulence factor enabling resistance to neutrophil attack.
- Understanding M protein structure is crucial for combating streptococcal infections.
Purpose of the Study:
- To analyze the complete amino acid sequence and structural characteristics of M6 protein.
- To investigate the conserved structural elements within M proteins.
Main Methods:
- Complete DNA sequencing of the M6 gene.
- Predictive secondary structure analysis of the M6 protein sequence.
- Sequence alignment of M6 and M5 proteins.
Main Results:
- M6 protein exhibits a coiled-coil structure with an alpha-helical rod domain divided into three subdomains.
- Identified conserved nonpolar residues forming the heptad periodicity essential for coiled-coil stability.
- 42% amino acid identity between M6 and M5 N-terminal regions, particularly in core structural residues.
Conclusions:
- M proteins share a conserved structural framework, featuring a central coiled-coil rod domain and variable end domains.
- Structural conservation suggests a fundamental molecular architecture underlying the function of diverse M proteins.
- This basic scheme provides insights into M protein evolution and function in streptococcal pathogenesis.