Molecular characterization of novel immunodominant molybdenum cofactor biosynthesis protein C1 (Rv3111) from Mycobacterium tuberculosis H37Rv

Biochim Biophys Acta. 2016 Apr;1860(4):694-707. doi: 10.1016/j.bbagen.2016.01.004. Epub 2016 Jan 13.

Abstract

Background: In the molybdenum cofactor biosynthesis pathway, MoaA and MoaC catalyze the first step of transformation of GTP to cPMP. In M. tuberculosis H37Rv, three different genes (Rv3111, Rv0864 and Rv3324c) encode for MoaC homologs. Out of these three only MoaC1 (Rv3111) is secretory in nature.

Methods: We have characterized MoaC1 protein through biophysical, in-silico, and immunological techniques.

Results: We have characterized the conformation and thermodynamic stability of MoaC1, and have established its secretory nature by demonstrating the presence of anti-MoaC1 antibodies in human tuberculosis patients' sera. Further, MoaC1 elicited a dominant Th1 immune response in mice characterized by increased induction of IL-2 and IFN-γ.

Conclusion: Integrating these results, we conclude that MoaC1 is a structured secretory protein capable of binding with GTP and eliciting induced immune response.

General significance: This study would be useful for the development of vaccines against tuberculosis and to improve methods used for diagnosis of tuberculosis.

Keywords: MoCo biosynthesis; MoaC1; Mycobacterium tuberculosis; Rv3111; Th1/Th2 cytokine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Proteins* / chemistry
  • Bacterial Proteins* / genetics
  • Bacterial Proteins* / immunology
  • Female
  • Genes, Bacterial
  • Humans
  • Interferon-gamma / immunology*
  • Interleukin-2 / immunology*
  • Male
  • Mice
  • Mycobacterium tuberculosis* / chemistry
  • Mycobacterium tuberculosis* / genetics
  • Mycobacterium tuberculosis* / immunology
  • Protein Stability
  • Sequence Homology, Amino Acid
  • Th1 Cells / immunology*
  • Tuberculosis Vaccines / chemistry
  • Tuberculosis Vaccines / genetics
  • Tuberculosis Vaccines / immunology

Substances

  • Bacterial Proteins
  • Interleukin-2
  • Tuberculosis Vaccines
  • Interferon-gamma