title: Zinc regulates a switch between primary and alternative S18 ribosomal proteins in Mycobacterium tuberculosis.
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.
authors: Division of Infectious Diseases, Boston Children's Hospital/Harvard Medical School, Boston, MA.|Department of Microbiology, University of Hawaii at Manoa, Honolulu, HI.
authors: Sladjana
authors: S
authors: Prisic
authors: Department of Pathology, Boston Children's Hospital/Harvard Medical School, Boston, MA.
authors: Hyonson
authors: H
authors: Hwang
authors: Department of Microbiology, University of Hawaii at Manoa, Honolulu, HI.
authors: Allexa
authors: A
authors: Dow
authors: Department of Pathology, Boston Children's Hospital/Harvard Medical School, Boston, MA.
authors: Omar
authors: O
authors: Barnaby
authors: Department of Microbiology, University of Hawaii at Manoa, Honolulu, HI.
authors: Tenny S
authors: TS
authors: Pan
authors: Department of Microbiology, University of Hawaii at Manoa, Honolulu, HI.
authors: Jaymes A
authors: JA
authors: Lonzanida
authors: Center for Structural Biology, Vanderbilt University, Nashville, TN, USA.
authors: Walter J
authors: WJ
authors: Chazin
authors: Department of Pathology, Boston Children's Hospital/Harvard Medical School, Boston, MA.
authors: Hanno
authors: H
authors: Steen
authors: Division of Infectious Diseases, Boston Children's Hospital/Harvard Medical School, Boston, MA.
authors: Robert N
authors: RN
authors: Husson
mesh_terms: D015964:Gene Expression Regulation, Bacterial; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000378:metabolism*; D012329:RNA, Bacterial / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D012335:RNA, Ribosomal / Q000235:genetics / Q000378:metabolism; D038601:Ribosomal Protein S6 / Q000235:genetics / Q000378:metabolism; D012269:Ribosomal Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015032:Zinc / Q000378:metabolism*
chemical_list: D012329:RNA, Bacterial; D012335:RNA, Ribosomal; D038601:Ribosomal Protein S6; D012269:Ribosomal Proteins; C041184:ribosomal protein S18; D015032:Zinc