scholarly journals Tropomyosin-like seven residue periodicity in three immunologically distinct streptococal M proteins and its implications for the antiphagocytic property of the molecule.

1980 ◽  
Vol 151 (3) ◽  
pp. 695-708 ◽  
Author(s):  
B N Manjula ◽  
V A Fischetti
Keyword(s):  
Tertiary Structure ◽  
Coiled Coil ◽  
Distinct Group ◽  
Structural Similarity ◽  
Amino Acid Residues ◽  
Conserved Residues ◽  
M Proteins ◽  
Significant Homology ◽  
Group A ◽  
The Common

Partial sequences of three immunologically distinct group A streptococcal M proteins (M5, M6, and M24) revealed significant homology with each other, certain amino acid residues being conserved within the three molecules. In addition, a common feature of the sequenced regions of these M proteins was their high alpha-helical potential and the presence of a repeating seven residue periodicity that is characteristic of the double helical coiled-coil molecule, tropomyosin. The existence of a tropomyosin-like seven residue periodicity strongly suggests that regions of these three M proteins may participate in intra- and/or intermolecular coiled-coil interactions. Because of the constraints imposed by such a repeating periodicity, certain conserved residues within the M proteins would occupy spatially equivalent positions in the tertiary structure of these molecules. This common characteristic could play an important role in the common antiphagocytic property of the immunologically diverse M molecules. In addition to similarities in the secondary structure of M proteins and tropomyosin, significant sequence homology has also been observed between certain regions of these molecules with up to 50% identical residues. As a result of the striking structural similarity with tropomyosin, M proteins may play a regulatory role in the contractile mechanisms involved in phagocytosis.

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.

scholarly journals Crystal structure of theMSMEG_4306gene product fromMycobacterium smegmatis

2018 ◽  
Vol 74 (3) ◽  
pp. 166-173
Author(s):  
Adarsh Kumar ◽  
Subramanian Karthikeyan
Keyword(s):  
Crystal Structure ◽  
Coiled Coil ◽  
Structural Similarity ◽  
Data Bank ◽  
Zinc Ion ◽  
Terminal Region ◽  
Amino Acid Residues ◽  
Secretion Systems ◽  
C Terminus ◽  
Zinc Ribbon

TheMSMEG_4306gene fromMycobacterium smegmatisencodes a protein of unknown function with 242 amino-acid residues that contains a conserved zinc-ribbon domain at its C-terminus. Here, the crystal structure of MSMEG_4306 determined by the single-wavelength anomalous dispersion method using just one zinc ion co-purified with the protein is reported. The crystal structure of MSMEG_4306 shows a coiled-coil helix domain in the N-terminal region and a zinc-ribbon domain in the C-terminal region. A structural similarity search against the Protein Data Bank using MSMEG_4306 as a query revealed two similar structures, namely CT398 fromChlamydia trachomatisand HP0958 fromHelicobacter pylori, although they share only ∼15% sequence identity with MSMEG_4306. Based on comparative analysis, it is predicted that MSMEG_4306 may be involved in secretion systems, possibly by interacting with multiple proteins or nucleic acids.

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 Identification and Characterization of a Novel Secreted Immunoglobulin Binding Protein from Group A Streptococcus

2001 ◽  
Vol 69 (8) ◽  
pp. 4851-4857 ◽  
Author(s):  
Peter K. Fagan ◽  
Dieter Reinscheid ◽  
Birgit Gottschalk ◽  
Gursharan S. Chhatwal
Keyword(s):  
Binding Proteins ◽  
Group A Streptococcus ◽  
Binding Protein ◽  
Coiled Coil ◽  
Invasive Disease ◽  
Local Similarity ◽  
M Proteins ◽  
Immunoglobulin Binding Protein ◽  
Group A ◽  
Immunoglobulin Binding

ABSTRACT Immunoglobulin binding proteins are one of several pathogenicity factors which have been associated with invasive disease caused by group A streptococci. The surface-bound M and M-like proteins ofStreptococcus pyogenes are the most characterized of these immunoglobulin binding proteins, and in most cases they bind only a single antibody class. Here we report the identification of a novel non-M-type secreted protein, designated SibA (for secreted immunoglobulin binding protein from group A streptococcus), which binds all immunoglobulin G (IgG) subclasses, the Fc and Fab fragments, and also IgA and IgM. SibA has no significant sequence homology to any M-related proteins, is not found in the vir regulon, and contains none of the characteristic M-protein regions, such as the A or C repeats. Like M proteins, however, SibA does have relatively high levels of alanine, lysine, glutamic acid, leucine, and glycine. SibA and M proteins also share an alpha-helical N-terminal secondary structure which has been previously implicated in immunoglobulin binding in M proteins. Evidence presented here indicates that this is also the case for SibA. SibA also has regions of local similarity with other coiled-coil proteins such as Listeria monocytogenes P45 autolysin, human myosin heavy chain, macrogolgin, and Schistoma mansoni paramyosin, some of which are of potential significance since cross-reactive antibodies between myosin proteins and M proteins have been implicated in the development of the autoimmune sequelae of streptococcal disease.

scholarly journals Coiled-coil destabilizing residues in the group A Streptococcus M1 protein are required for functional interaction

2016 ◽  
Vol 113 (34) ◽  
pp. 9515-9520 ◽  
Author(s):  
Chelsea M. Stewart ◽  
Cosmo Z. Buffalo ◽  
J. Andrés Valderrama ◽  
Anna Henningham ◽  
Jason N. Cole ◽  
...  
Keyword(s):  
Group A Streptococcus ◽  
Conformational Dynamics ◽  
Coiled Coil ◽  
Bacterial Pathogen ◽  
Intrinsically Disordered ◽  
M1 Protein ◽  
M Proteins ◽  
Group A ◽  
Multiple Conformations ◽  
Major Surface

The sequences of M proteins, the major surface-associated virulence factors of the widespread bacterial pathogen group A Streptococcus, are antigenically variable but have in common a strong propensity to form coiled coils. Paradoxically, these sequences are also replete with coiled-coil destabilizing residues. These features are evident in the irregular coiled-coil structure and thermal instability of M proteins. We present an explanation for this paradox through studies of the B repeats of the medically important M1 protein. The B repeats are required for interaction of M1 with fibrinogen (Fg) and consequent proinflammatory activation. The B repeats sample multiple conformations, including intrinsically disordered, dissociated, as well as two alternate coiled-coil conformations: a Fg-nonbinding register 1 and a Fg-binding register 2. Stabilization of M1 in the Fg-nonbinding register 1 resulted in attenuation of Fg binding as expected, but counterintuitively, so did stabilization in the Fg-binding register 2. Strikingly, these register-stabilized M1 proteins gained the ability to bind Fg when they were destabilized by a chaotrope. These results indicate that M1 stability is antithetical to Fg interaction and that M1 conformational dynamics, as specified by destabilizing residues, are essential for interaction. A “capture-and-collapse” model of association accounts for these observations, in which M1 captures Fg through a dynamic conformation and then collapses into a register 2-coiled coil as a result of stabilization provided by binding energy. Our results support the general conclusion that destabilizing residues are evolutionarily conserved in M proteins to enable functional interactions necessary for pathogenesis.

The crystal structure of myoglobin. VI. Seal myoglobin

1960 ◽  
Vol 258 (1293) ◽  
pp. 181-201 ◽  
Keyword(s):  
Tertiary Structure ◽  
Heavy Atom ◽  
Three Dimensional ◽  
Sperm Whale ◽  
Fourier Synthesis ◽  
Heavy Atoms ◽  
Isomorphous Replacement ◽  
Unit Cells ◽  
The Common ◽  
Sperm Whale Myoglobin

Myoglobin from the common seal ( Phoca vitulina ) when crystallized from ammonium sulphate forms monoclinic crystals with space group the unit cell, a = 57·9Å, b = 29·6Å, c = 106·4Å, β = 102°15', contains four molecules. The method of isomorphous replacement has been used in an investigation of the centrosymmetric b -axis projection in which it has been possible to determine signs for nearly all the h0l reflexions having spacings greater than 4Å. Three independent heavy-atom derivatives were employed and the signs so determined have been used to compute a map of the electron density projected on the (010) plane. This projection has been interpreted in terms of the molecule of sperm-whale myoglobin, as deduced by Bodo, Dintzis, Kendrew & Wyckoff (1959) from a three-dimensional Fourier synthesis to 6Å resolution. The results of the interpretation show that the two myoglobin molecules are very similar in form (tertiary structure) in spite of the differences in their amino-acid composition. The relative orientation of the two unit cells with respect to the myoglobin molecule is given and a comparison is made of the positions of the heavy atoms in each molecule.

Immunological Mimicry between Retinal S-Antigen and Group A Streptococcal M Proteins

Autoimmunity ◽  
1995 ◽  
Vol 22 (2) ◽  
pp. 95-106 ◽  
Author(s):  
Michael P. Lerner ◽  
Larry A. Donoso ◽  
Robert E. Nordquist ◽  
Madeleine W. Cunningham
Keyword(s):  
M Proteins ◽  
Group A

Dirty Work and Dirtier Work: Differences in Countering Physical, Social, and Moral Stigma

2014 ◽  
Vol 10 (1) ◽  
pp. 81-108 ◽  
Author(s):  
Blake E. Ashforth ◽  
Glen E. Kreiner
Keyword(s):  
Distinct Group ◽  
The Other ◽  
Future Research ◽  
Identity Threat ◽  
Dirty Work ◽  
Exotic Dancers ◽  
Organization Level ◽  
Group A

The literature on dirty work has focused on what physically (e.g., garbage collectors), socially (e.g., addiction counsellors), and morally (e.g., exotic dancers) stigmatized occupations have in common, implying that dirty work is a relatively monolithic construct. In this article, we focus on thedifferencesbetween these three forms of dirty work and how occupational members collectively attempt to counter the particular stigma associated with each. We argue that the largest differences are between moral dirty work and the other two forms; if physical and social dirty work tend to be seen as more necessary than evil, then moral dirty work tends to be seen as more evil than necessary. Moral dirty work typically constitutes a graver identity threat to occupational members, fostering greater entitativity (a sense of being a distinct group), a greater reliance on members as social buffers, and a greater use of condemning condemners and organization-level defensive tactics. We develop a series of propositions to formalize our arguments and suggest how this more nuanced approach to studying dirty work can stimulate and inform future research.

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