Format

Send to

Choose Destination
Mol Microbiol. 2015 Jul;97(2):263-80. doi: 10.1111/mmi.13022. Epub 2015 May 15.

Zinc regulates a switch between primary and alternative S18 ribosomal proteins in Mycobacterium tuberculosis.

Author information

1
Division of Infectious Diseases, Boston Children's Hospital/Harvard Medical School, Boston, MA.
2
Department of Microbiology, University of Hawaii at Manoa, Honolulu, HI.
3
Department of Pathology, Boston Children's Hospital/Harvard Medical School, Boston, MA.
4
Center for Structural Biology, Vanderbilt University, Nashville, TN, USA.

Abstract

The Mycobacterium tuberculosis genome encodes five putative 'alternative' ribosomal proteins whose expression is repressed at high Zn(2+) concentration. Each alternative protein has a primary homologue that is predicted to bind Zn(2+). We hypothesized that zinc triggers a switch between these paired homologous proteins and therefore chose one of these pairs, S18-1/S18-2, to study mechanisms of the predicted competition for their incorporation into ribosomes. Our data show that Zn(2+)-depletion causes accumulation of both S18-2 mRNA and protein. In contrast, S18-1 mRNA levels are unchanged to slightly elevated under Zn(2+)-limited conditions. However, the amount of S18-1 protein is markedly decreased. We further demonstrate that both S18 proteins interact with ribosomal protein S6, a committed step in ribosome biogenesis. Zn(2+) is absolutely required for the S18-1/S6 interaction while it is dispensable for S18-2/S6 dimer formation. These data suggest a model in which S18-1 is the dominant ribosome constituent in high zinc conditions, e.g. inside of phagosomes, but that it can be replaced by S18-2 when zinc is deficient, e.g. in the extracellular milieu. Consequently, Zn(2+)-depletion may serve as a signal for building alternative ribosomes when M. tuberculosis is released from macrophages, to allow survival in the extracellular environment.

PMID:
25858183
PMCID:
PMC4548965
DOI:
10.1111/mmi.13022
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center