| Title |
Molecular Evolutionary Constraints that Determine the Avirulence State of Clostridium botulinum C2 Toxin
|
|---|---|
| Published in |
Journal of Molecular Evolution, April 2017
|
| DOI | 10.1007/s00239-017-9791-y |
| Pubmed ID | |
| Authors |
A. Prisilla, R. Prathiviraj, P. Chellapandi |
| Abstract |
Clostridium botulinum (group-III) is an anaerobic bacterium producing C2 toxin along with botulinum neurotoxins. C2 toxin is belonged to binary toxin A family in bacterial ADP-ribosylation superfamily. A structural and functional diversity of binary toxin A family was inferred from different evolutionary constraints to determine the avirulence state of C2 toxin. Evolutionary genetic analyses revealed evidence of C2 toxin cluster evolution through horizontal gene transfer from the phage or plasmid origins, site-specific insertion by gene divergence, and homologous recombination event. It has also described that residue in conserved NAD-binding core, family-specific domain structure, and functional motifs found to predetermine its virulence state. Any mutational changes in these residues destabilized its structure-function relationship. Avirulent mutants of C2 toxin were screened and selected from a crucial site required for catalytic function of C2I and pore-forming function of C2II. We found coevolved amino acid pairs contributing an essential role in stabilization of its local structural environment. Avirulent toxins selected in this study were evaluated by detecting evolutionary constraints in stability of protein backbone structure, folding and conformational dynamic space, and antigenic peptides. We found 4 avirulent mutants of C2I and 5 mutants of C2II showing more stability in their local structural environment and backbone structure with rapid fold rate, and low conformational flexibility at mutated sites. Since, evolutionary constraints-free mutants with lack of catalytic and pore-forming function suggested as potential immunogenic candidates for treating C. botulinum infected poultry and veterinary animals. Single amino acid substitution in C2 toxin thus provides a major importance to understand its structure-function link, not only of a molecule but also of the pathogenesis. |
X Demographics
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Uganda | 1 | 25% |
| United Kingdom | 1 | 25% |
| Unknown | 2 | 50% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 3 | 75% |
| Scientists | 1 | 25% |
Mendeley readers
The data shown below were compiled from readership statistics for 9 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 9 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 3 | 33% |
| Researcher | 3 | 33% |
| Student > Bachelor | 1 | 11% |
| Student > Master | 1 | 11% |
| Unknown | 1 | 11% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 3 | 33% |
| Biochemistry, Genetics and Molecular Biology | 2 | 22% |
| Environmental Science | 1 | 11% |
| Nursing and Health Professions | 1 | 11% |
| Materials Science | 1 | 11% |
| Other | 0 | 0% |
| Unknown | 1 | 11% |
Attention Score in Context
This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 21 September 2017.
All research outputs
#13,854,210
of 22,962,258 outputs
Outputs from Journal of Molecular Evolution
#1,078
of 1,447 outputs
Outputs of similar age
#164,558
of 309,562 outputs
Outputs of similar age from Journal of Molecular Evolution
#5
of 11 outputs
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