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Sequence homology of group A streptococcal Pep M5 protein with other coiled-coil proteins
Abstract:
Group A streptococcal Pep M5 protein, an antiphagocytic determinant of the bacteria, is an alpha-helical coiled-coil molecule, and exhibits significant sequence homology with tropomyosin and myosin, but to a lesser degree with other coiled-coil proteins. Moreover, Pep M5 is more homologous to myosin than to tropomyosin, and the homologies are more numerous between the C-terminal domain of the Pep M5 protein and the S2 fragment of myosin. The C-terminal domain of the Pep M5 protein exhibits extensive sequence identity with the C-terminal region of Pep M6 molecule, another M protein serotype. Thus, regions within two M protein serotypes are homologous to the S2 region of the myosin molecule. These observations are consistent with the immunological findings of other investigators and thus may explain some of the previously reported immunological cross-reactions between antigens of the group A streptococcus and mammalian heart tissue.
Insights
Group A streptococcal Pep M5 protein shares structural similarities with human myosin and tropomyosin. This molecular mimicry may explain cross-reactions between streptococcal antigens and heart tissue.
Area of Science:
- Microbiology
- Molecular Biology
- Immunology
Background:
- Group A Streptococcus (GAS) is a significant human pathogen.
- The M protein, specifically Pep M5, is a key antiphagocytic factor produced by GAS.
- Previous studies noted cross-reactivity between GAS antigens and mammalian heart tissue.
Purpose of the Study:
- To investigate the molecular structure of the Group A streptococcal Pep M5 protein.
- To compare the sequence homology of Pep M5 with other coiled-coil proteins, particularly myosin and tropomyosin.
- To explore the potential molecular basis for observed immunological cross-reactions.
Main Methods:
- Sequence analysis of the Pep M5 protein.
- Comparative sequence homology studies with tropomyosin, myosin, and other coiled-coil proteins.
- Examination of homology between Pep M5 and Pep M6, another M protein serotype.
Main Results:
- Pep M5 protein is an alpha-helical coiled-coil molecule.
- Pep M5 exhibits significant sequence homology with tropomyosin and myosin, more so with myosin.
- Homologies are concentrated in the C-terminal domain of Pep M5 and the S2 fragment of myosin.
- The C-terminal domain of Pep M5 shows extensive sequence identity with the C-terminal region of Pep M6.
Conclusions:
- The structural similarities between Pep M5 and human myosin/tropomyosin provide a molecular explanation for cross-reactivity.
- Regions within different M protein serotypes (Pep M5 and Pep M6) are homologous to the myosin S2 region.
- These findings support the hypothesis of molecular mimicry contributing to autoimmune responses against heart tissue in some streptococcal infections.