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TitleZinc depletion induces ribosome hibernation in mycobacteria.
Journal, issue, pagesProc Natl Acad Sci U S A, Vol. 115, Issue 32, Page 8191-8196, Year 2018
Publish dateAug 7, 2018
AuthorsYunlong Li / Manjuli R Sharma / Ravi K Koripella / Yong Yang / Prem S Kaushal / Qishan Lin / Joseph T Wade / Todd A Gray / Keith M Derbyshire / Rajendra K Agrawal / Anil K Ojha /
PubMed AbstractBacteria respond to zinc starvation by replacing ribosomal proteins that have the zinc-binding CXXC motif (C+) with their zinc-free (C-) paralogues. Consequences of this process beyond zinc ...Bacteria respond to zinc starvation by replacing ribosomal proteins that have the zinc-binding CXXC motif (C+) with their zinc-free (C-) paralogues. Consequences of this process beyond zinc homeostasis are unknown. Here, we show that the C- ribosome in is the exclusive target of a bacterial protein Y homolog, referred to as mycobacterial-specific protein Y (MPY), which binds to the decoding region of the 30S subunit, thereby inactivating the ribosome. MPY binding is dependent on another mycobacterial protein, MPY recruitment factor (MRF), which is induced on zinc depletion, and interacts with C- ribosomes. MPY binding confers structural stability to C- ribosomes, promoting survival of growth-arrested cells under zinc-limiting conditions. Binding of MPY also has direct influence on the dynamics of aminoglycoside-binding pockets of the C- ribosome to inhibit binding of these antibiotics. Together, our data suggest that zinc limitation leads to ribosome hibernation and aminoglycoside resistance in mycobacteria. Furthermore, our observation of the expression of the proteins of C- ribosomes in in a mouse model of infection suggests that ribosome hibernation could be relevant in our understanding of persistence and drug tolerance of the pathogen encountered during chemotherapy of TB.
External linksProc Natl Acad Sci U S A / PubMed:30038002 / PubMed Central
MethodsEM (single particle)
Resolution3.42 - 3.6 Å
Structure data

EMDB-8932, PDB-6dzi:
Cryo-EM Structure of Mycobacterium smegmatis 70S C(minus) ribosome 70S-MPY complex
Method: EM (single particle) / Resolution: 3.46 Å

EMDB-8934, PDB-6dzk:
Cryo-EM Structure of Mycobacterium smegmatis C(minus) 30S ribosomal subunit with MPY
Method: EM (single particle) / Resolution: 3.6 Å

EMDB-8937, PDB-6dzp:
Cryo-EM Structure of Mycobacterium smegmatis C(minus) 50S ribosomal subunit
Method: EM (single particle) / Resolution: 3.42 Å

Source
  • mycobacterium smegmatis str. mc2 155 (bacteria)
  • mycobacterium smegmatis (strain atcc 700084 / mc(2)155) (bacteria)
  • mycobacterium smegmatis (bacteria)
KeywordsRIBOSOME / Hibernation factor complex

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