6DZK

Cryo-EM Structure of Mycobacterium smegmatis C(minus) 30S ribosomal subunit with MPY

Summary for 6DZK

• Entry DOI: 10.2210/pdb6dzk/pdb
• Related: 5O5J
• EMDB information: 3748 8934
• Descriptor: 16S rRNA, 30S ribosomal protein S10, 30S ribosomal protein S11, ... (23 entities in total)
• Functional Keywords: hibernation factor complex, ribosome
• Biological source: Mycobacterium smegmatis str. MC2 155; More
• Total number of polymer chains: 23
• Total formula weight: 829164.37

Authors

Sharma, M.R.,Li, Y.,Korripella, R.,Yang, Y.,Kaushal, P.S.,Lin, Q.,Wade, J.T.,Gray, A.G.,Derbyshire, K.M.,Agrawal, R.K.,Ojha, A. (deposition date: 2018-07-05, release date: 2018-09-19, Last modification date: 2024-03-13)

Primary citation

Li, Y.,Sharma, M.R.,Koripella, R.K.,Yang, Y.,Kaushal, P.S.,Lin, Q.,Wade, J.T.,Gray, T.A.,Derbyshire, K.M.,Agrawal, R.K.,Ojha, A.K.
Zinc depletion induces ribosome hibernation in mycobacteria.
Proc. Natl. Acad. Sci. U.S.A., 115:8191-8196, 2018

PubMed Abstract: 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.

PubMed: 30038002
DOI: 10.1073/pnas.1804555115

Experimental method

ELECTRON MICROSCOPY (3.6 Å)