Title

Structural inferences for Cholera toxin mutations in Vibrio cholerae 

Authors

Gunasagaran Shamini^{1, 5}, Manickam Ravichandran¹, John T Sinnott^{2, 3}, Charurut Somboonwit^{2, 3}, Harcharan S Siddhu¹, Paul Shapshak^{2, 4}, Pandjassarame Kangueane^{1, 5}* 

Affiliation

¹Department of Biotechnology, AIMST University, Semeling 08100, Kedah, Malaysia; ²Division of Infectious Disease, Department of Internal Medicine, Tampa General Hospital, University of South Florida, College of Medicine, Tampa, Florida 33606, USA; ³Clinical Research Unit, Hillsborough Health Department, Tampa, Florida 33602, USA; ⁴Department of Psychiatry and Behavioral Medicine, University of South Florida, College of Medicine, Tampa, Florida 33613, USA; ⁵Biomedical Informatics, Pondicherry, India 607402  

Email

kangueane@bioinformation.net; *Corresponding author  

Phone

+6012 436 2581

Article Type

Hypothesis

Date

Received January 20, 2011; Accepted February 01, 2011; Published March 02, 2011
 

Cholera is a global disease that has persisted for millennia. The cholera toxin (CT) from Vibrio cholerae is responsible for the clinical symptoms of cholera. This toxin is a hetero-hexamer (AB₅) complex consisting of a subunit A (CTA) with a pentamer (B₅) of subunit B (CTB). The importance of the AB₅ complex for pathogenesis is established for the wild type O1 serogroup using known structural and functional data. However, its role is not yet documented in other known serogroups harboring sequence level residue mutations. The sequences for the toxin from different serogroups are available in GenBank (release 177). Sequence analysis reveals mutations at several sequence positions in the toxin across serogroups. Therefore, it is of interest to locate the position of these mutations in the AB₅ structure to infer complex assembly for its functional role in different serogroups. We show that mutations in the CTA are at the solvent exposed regions of the AB₅ complex, whereas those in the CTB are at the CTB/CTB interface of the homo-pentamer complex. Thus, the role of mutations at the CTB/CTB interface for B₅ complex assembly is implied. It is observed that these mutations are often non-synonymous (e.g. polar to non-polar or vice versa). The formation of the AB₅ complex involves inter-subunit residue-residue interactions at the protein-protein interfaces. Hence, these mutations, at the structurally relevant positions, are of importance for the understanding of pathogenesis by several serogroups. This is also of significance in the improvement of recombinant CT protein complex analogs for vaccine design and their use against multiple serogroups. 

Keywords

Cholera toxin (CT), Vibrio cholerae, O1/O139, non O1/O139, mutation, protein-protein interfaces
 

Citation

Shamini et al. Bioinformation 6(1): 1- 9 (2011)

Edited by

VS Mathura

ISSN

0973-2063

Publisher

Biomedical Informatics

License

This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.