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-Structure paper
タイトル | Zinc depletion induces ribosome hibernation in mycobacteria. |
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ジャーナル・号・ページ | Proc Natl Acad Sci U S A, Vol. 115, Issue 32, Page 8191-8196, Year 2018 |
掲載日 | 2018年8月7日 |
著者 | Yunlong 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 要旨 | 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 ...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. |
リンク | Proc Natl Acad Sci U S A / PubMed:30038002 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.42 - 3.6 Å |
構造データ | EMDB-8932, PDB-6dzi: |
由来 |
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キーワード | RIBOSOME / Hibernation factor complex |