Heptad motifs within the distal subdomain of the coiled-coil rod region of M protein from rheumatic fever and nephritis associated serotypes of group A streptococci are distinct from each other: Nucleotide sequence of the M57 gene and relation of the deduced amino acid sequence to other M proteins

1991 ◽  
Vol 10 (4) ◽  
pp. 369-384 ◽  
Author(s):  
B. N. Manjula ◽  
K. M. Khandke ◽  
T. Fairwell ◽  
W. A. Relf ◽  
K. S. Sriprakash
Keyword(s):  
Amino Acid ◽  
Nucleotide Sequence ◽  
Amino Acid Sequence ◽  
Rheumatic Fever ◽  
Coiled Coil ◽  
M Protein ◽  
Group A Streptococci ◽  
M Proteins ◽  
Group A

scholarly journals Antigenic domains of the streptococcal Pep M5 protein. Localization of epitopes crossreactive with type 6 M protein and identification of a hypervariable region of the M molecule.

1986 ◽  
Vol 163 (1) ◽  
pp. 129-138 ◽  
Author(s):  
B N Manjula ◽  
A S Acharya ◽  
T Fairwell ◽  
V A Fischetti
Keyword(s):  
Protein Localization ◽  
Hypervariable Region ◽  
Coiled Coil ◽  
M Protein ◽  
Terminal Domain ◽  
Coil Structure ◽  
M Proteins ◽  
Group A ◽  
Antigenic Domains ◽  
Antigenic Epitopes

Pep M5, the pepsin-derived N-terminal half of the group A streptococcal type 5 M protein exhibits immunologic crossreaction with type 6 M protein, localizing some of the M6-crossreactive epitope(s) within this segment of the M5 protein. Based on the amino acid sequence of the Pep M5 protein, two structurally distinct domains have been recognized within its coiled-coil structure. We have now found that peptides derived from both the structurally distinct domains of the Pep M5 protein contain antigenic epitopes. Furthermore, only the peptides from the C-terminal domain of the Pep M5 protein crossreacted with rabbit anti-M6 sera, whereas those from the N-terminal domain did not. Consistent with this, sequence analyses of the arginyl peptides of the Pep M6 protein, the pepsin-derived N-terminal half of the M6 protein, revealed extensive homology of some of these peptides with regions within the C-terminal domain of the Pep M5 molecule. While an arginyl peptide of the Pep M6 protein exhibits 84% homology with region 150-186 of the Pep M5 protein, the C-terminal hexadecapeptide of the Pep M6 protein is virtually identical with the corresponding region of the Pep M5 protein. These results are suggestive of conformational similarities in the region around the pepsin-susceptible site within the M5 and M6 proteins. In addition, one or more epitopes of the M5 protein that are crossreactive with the M6 protein may be placed close to the pepsin-susceptible site of the M5 protein. Previous studies have suggested the N-terminal half of the M proteins to be the variable part of the molecule among the different M protein serotypes. The present results suggest that the N-terminal quarter of the M protein may represent the hypervariable domain of the M molecule.

Towards a vaccine for rheumatic fever: identification of a conserved target epitope on M protein of group A streptococci

The Lancet ◽  
1994 ◽  
Vol 344 (8923) ◽  
pp. 639-642 ◽  
Author(s):  
S Pruksakorn ◽  
E Brandt ◽  
M.F Good ◽  
B Currie ◽  
D Martin ◽  
...  
Keyword(s):  
Rheumatic Fever ◽  
M Protein ◽  
Group A Streptococci ◽  
Target Epitope ◽  
Group A

scholarly journals Difference in the structural features of streptococcal M proteins from nephritogenic and rheumatogenic serotypes.

1987 ◽  
Vol 166 (1) ◽  
pp. 151-162 ◽  
Author(s):  
K M Khandke ◽  
T Fairwell ◽  
B N Manjula
Keyword(s):  
Tertiary Structure ◽  
Structural Information ◽  
Gel Filtration ◽  
Structural Features ◽  
Biologically Active ◽  
M Protein ◽  
Acute Glomerulonephritis ◽  
Group A Streptococci ◽  
M Proteins ◽  
Group A

The association of only certain M protein serotypes of group A streptococci with acute glomerulonephritis is very well recognized. Structural information on the M protein, a dimeric alpha-helical coiled-coil molecule, has come so far from three rheumatogenic serotypes, 5, 6, and 24. However, M proteins from the nephritogenic serotypes have not been well characterized. In the present study, we have isolated a biologically active 20,000 Mr pepsin fragment of type 49 M protein (PepM49), a nephritogenic serotype, and purified it to homogeneity using DEAE-Sephadex and gel filtration. The amino acid composition of PepM49 is similar to those of the rheumatogenic M protein serotypes PepM5, PepM6, and PepM24. However, the sequence of the NH2-terminal 60 residues of PepM49 shows little homology to any of these M protein serotypes, although the latter have significant homology among themselves. Nevertheless, PepM49 exhibits a strong heptad periodicity in its nonpolar residues, suggesting its overall conformational similarity with the other M molecules. During the course of the present studies, Moravek et al. (17) reported the NH2-terminal sequence of another M protein serotype, PepM1, which also does not exhibit much homology with the PepM5, PepM6, and PepM24 proteins. Our analysis of this sequence revealed that the PepM1 protein also exhibits a heptad periodicity of the nonpolar amino acids. A closer examination has revealed that the pattern of heptad periodicity in PepM49 and PepM1 proteins is more regular and more similar to each other than has been previously seen for the PepM5, PepM6, and PepM24 proteins. PepM1 is also a nephritogenic serotype. Taken together, these findings indicate an underlying conservation of the tertiary structure of the various M protein serotypes, despite the complexity in their antigenic variation and suggest that the nephritogenic M protein serotypes M1 and M49 may be further apart evolutionarily from the rheumatogenic serotypes 5, 6, and 24. The distinct differences in the structural features of the PepM1 and PepM49 proteins relative to the PepM5, PepM6, and PepM24 proteins are also suggestive of a correlation with the earlier broader classification of the group A streptococci into rheumatogenic and nephritogenic serotypes.

scholarly journals Multivalent Group A Streptococcal Vaccine Elicits Bactericidal Antibodies against Variant M Subtypes

2005 ◽  
Vol 12 (7) ◽  
pp. 833-836 ◽  
Author(s):  
James B. Dale ◽  
Thomas Penfound ◽  
Edna Y. Chiang ◽  
Valerie Long ◽  
Stanford T. Shulman ◽  
...  
Keyword(s):  
Wide Spectrum ◽  
Epidemiologic Studies ◽  
M Protein ◽  
Group A Streptococci ◽  
Protein Vaccine ◽  
Amino Terminal ◽  
M Proteins ◽  
Group A ◽  
Clinical Illness

ABSTRACT Group A streptococci cause a wide spectrum of clinical illness. One of several strategies for vaccine prevention of these infections is based on the type-specific M protein epitopes. A multivalent M protein-based vaccine containing type-specific determinants from 26 different M serotypes is now in clinical trials. Recent epidemiologic studies have shown that, within some serotypes, the amino-terminal M protein sequence may show natural variation, giving rise to subtypes. This raises the possibility that vaccine-induced antibodies against the parent type may not be as effective in promoting bactericidal killing of variant subtypes. In the present study we used rabbit antisera against the 26-valent M protein-based vaccine in bactericidal tests against M1, M3, and M5 streptococci, which were represented by multiple subtypes. We show that the vaccine antibodies effectively promoted in vitro bactericidal activity despite the fact that the M proteins contained naturally occurring variant sequences in the regions corresponding to the vaccine sequence. Our results show that the variant M proteins generally do not result in significant differences in opsonization promoted by rabbit antisera raised against the 26-valent vaccine, suggesting that a multivalent M protein vaccine may not permit variant subtypes of group A streptococci to escape in a highly immunized population.

Characterization of group A streptococcal M-proteins purified by two methods

1976 ◽  
Vol 22 (8) ◽  
pp. 1072-1082
Author(s):  
David C. Straus ◽  
Charles F. Lange
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Gel Electrophoresis ◽  
Polyacrylamide Gel Electrophoresis ◽  
Molecular Size ◽  
M Protein ◽  
M Proteins ◽  
Group A ◽  
Terminal Amino ◽  
High Concentrations

Ten different group A streptococcal M-protein preparations purified by trichloroacetic acid precipitation and three M-protein preparations purified by cellulose chromatography were examined by SDS and polyacrylamide gel electrophoresis, and analyzed for amino acid composition and N-terminal amino acids. Fingerprinting (both tryptic and chymotryptic) was performed on the cellulose-purified preparations of M1, M12, and M29 proteins which showed these proteins to be structurally related. Trypsin produced maps with 37 to 42 peptides, whereas chymotrypsin digestion resulted in 8 to 12 peptides, depending on the M-type. Sequencing was performed on the M12 protein and tentative identification of nine N-terminal amino acids was made. Molecular weights of the cellulose and TCA-purified M-proteins were determined by SDS gel electrophoresis and chromatography on G-200 Sephadex, with comparable results, indicating molecular size of at least 23 000. The amino acid analyses of the 10 TCA-purified proteins followed the patterns established for M-proteins, with high concentrations of lysine, aspartic acid, glutamic acid, alanine, and leucine. All 10 proteins had L-alanine as their N-terminal amino acid. Evidence for a one way cross-reaction between type 1 and type 29 streptococci was also found.

Can class I epitope of M protein be a diagnostic marker for rheumatic fever in populations endemic for group A streptococci?

The Lancet ◽  
1998 ◽  
Vol 351 (9119) ◽  
pp. 1860 ◽  
Author(s):  
Evelyn R Brandt ◽  
Bart Currie ◽  
Layla Mammo ◽  
Sumalee Pruksakorn ◽  
Michael F Good
Keyword(s):  
Rheumatic Fever ◽  
Diagnostic Marker ◽  
Class I ◽  
M Protein ◽  
Group A Streptococci ◽  
Group A

scholarly journals Reactivity of Rheumatic Fever and Scarlet Fever Patients' Sera with Group A Streptococcal M Protein, Cardiac Myosin, and Cardiac Tropomyosin: a Retrospective Study

2000 ◽  
Vol 68 (12) ◽  
pp. 7132-7136 ◽  
Author(s):  
Kevin F. Jones ◽  
Stephen S. Whitehead ◽  
Madeleine W. Cunningham ◽  
Vincent A. Fischetti
Keyword(s):  
Retrospective Study ◽  
Rheumatic Fever ◽  
Scarlet Fever ◽  
Acute Rheumatic Fever ◽  
M Protein ◽  
Group A Streptococci ◽  
Cardiac Myosin ◽  
Streptococcal M Protein ◽  
Group A ◽  
Low Levels

ABSTRACT Archived sera (collected in 1946) from acute rheumatic fever (ARF) and untreated scarlet fever and/or pharyngitis patients were reacted with streptococcal M protein, cardiac myosin, and cardiac tropomyosin. Except for very low levels to tropomyosin, antibodies to other antigens were not elevated in the sera of ARF patients relative to those of non-ARF patients, even though there was roughly equivalent exposure to group A streptococci. This suggests that antibodies to these molecules may not play a central role in the induction of ARF.

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