Structural insights into species-specific features of the ribosome from the human pathogen Mycobacterium tuberculosis

Yang, Kailu; Chang, Jeng-Yih; Zhao, Chunhe; Li, Xiaojun; Meng, Ran; Duan, Lei; Thongchol, Jirapat; Jakana, Joanita; Huwe, Christoph M.; Sacchettini, James C.; Zhang, Junjie

doi:10.1093/nar/gkx785

Cited by 71 publications

(81 citation statements)

References 75 publications

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“…Mycobacteria, for example, have very distinct translational features compared with the model E. coli system (39, 48, 49). Recent structural information about the mycobacterial ribosome identified new ribosomal protein subunits, but these new subunits, bL37 and bS22 were not present in all ribosomes identified by cryo-electron microscopy (34, 50, 51).…”

Section: Discussionmentioning

confidence: 98%

Selective translation by alternative bacterial ribosomes

Chen

et al. 2019

Preprint

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Section: Discussionmentioning

confidence: 98%

Selective translation by alternative bacterial ribosomes

Chen

et al. 2019

Preprint

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“…89 In M. tuberculosis the 50S subunit is up made of rRNA 23S, rRNA 5S, and about 30 rProteins, while the 30S subunit is composed of rRNA 16S and about 20 rProteins. 90 rRNA is the major functional core of RNA since it carries out three major functions, catalysis of peptide-bond formation, decoding of mRNA, and translocation of mRNA and tRNA after completion of peptide-bond formation. 90 During initiation of translation, tRNA carrying formylmethionine binds to the P-site of 50S subunit.…”

Section: Interaction Of Linezolid With 50s Ribosomal Subunitmentioning

confidence: 99%

“…90 rRNA is the major functional core of RNA since it carries out three major functions, catalysis of peptide-bond formation, decoding of mRNA, and translocation of mRNA and tRNA after completion of peptide-bond formation. 90 During initiation of translation, tRNA carrying formylmethionine binds to the P-site of 50S subunit. The P-site is the binding site for peptidyl-tRNA and an adjacent A-site is the binding site for incoming aa-tRNA.…”

Section: Interaction Of Linezolid With 50s Ribosomal Subunitmentioning

confidence: 99%

An overview of new antitubercular drugs, drug candidates, and their targets

Bahuguna

Rawat

2019

Medicinal Research Reviews

140

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The causative agent of tuberculosis (TB), Mycobacterium tuberculosis and more recently totally drug‐resistant strains of M. tuberculosis, display unique mechanisms to survive in the host. A four‐drug treatment regimen was introduced 40 years ago but the emergence of multidrug‐resistance and more recently TDR necessitates the identification of new targets and drugs for the cure of M. tuberculosis infection. The current efforts in the drug development process are insufficient to completely eradicate the TB epidemic. For almost five decades the TB drug development process remained stagnant. The last 10 years have made sudden progress giving some new and highly promising drugs including bedaquiline, delamanid, and pretomanid. Many of the candidates are repurposed compounds, which were developed to treat other infections but later, exhibited anti‐TB properties also. Each class of drug has a specific target and a definite mode of action. These targets are either involved in cell wall biosynthesis, protein synthesis, DNA/RNA synthesis, or metabolism. This review discusses recent progress in the discovery of newly developed and Food and Drug Administration approved drugs as well as repurposed drugs, their targets, mode of action, drug‐target interactions, and their structure‐activity relationship.

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“…The density for bS21 was also not observed in the Ms and Mtb ribosome structures published recently [146][147][148]. bS21 is a late ribosome binding protein.…”

Section: Figure 315 R-protein Us16 Interaction With Us4 In Ms 30s (mentioning

confidence: 74%

“…In the genus Mycobacterium, a homolog of bS21 is present in Mycobacterium abscessus, an early mycobacterial species, and in Mtb. However, Mtb bS21 protein was not localized in the recently published 70S ribosome structure of Mtb [146]. Ms SSU r-proteins bS6, uS7, and uS14 are significantly shorter in length by more than 20 residues than their Ec homologs because of the truncation at Nor C-terminal (Table 3.2).…”

Section: Figure 315 R-protein Us16 Interaction With Us4 In Ms 30s (mentioning

confidence: 91%

Cryo-EM structure of the Mycobacterium smegmatis ribosome

Mishra¹

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vi 1.8.1 Mechanism of formation of hibernating ribosome dimers (100S ribosome) 1.8.2 Physiological significance of hibernating ribosome 1.9 Trans-translating Ribosome 1.9.1 Structure of tmRNA 1.9.2 The mechanism of trans-translation 1.9.3 Physiological significance of trans-translation 1.10 Mycobacterial Ribosome 1.11 Cryo-EM 1.12 Aim of this dissertation 2 Materials and Methods 2.1 Materials 2.1.1 Buffers, Media and Salts 2.1.2 Microbiology strains 2.1.3 Buffer Composition 2.1.4 Instruments and accessories 2.1.5 Computer tools and softwares 2.2 Methods 2.2.1 Purification of 70S ribosomes from M. smegmatis 2.2.2 Ribosome protein identification by SDS PAGE and Mass Spectrometry 2.2.3 Purification of 70S ribosomes from M. smegmatis growing in different growth phases 2.2.4 Cryo-Electron Microscopy 2.2.5 Cryo-EM Single Particle Analysis (Data Processing) 2.2.6 Current capabilities and limitations of cryo-EM and Single Particle Analysis 2.2.7 Cryo-EM imaging of M. smegmatis ribosome 2.2.8 Model building and refinement 2.2.9 Model validation 2.2.10 Figure generation vii 3 Results Cryo-EM structures of M. smegmatis ribosomes in different functional states 3.1 Purification profile of M. smegmatis ribosomes in log and stationary phase 3.2 Micrograph inspection 3.3 Image Processing 3.3.1 2D classification 3.3.2 3D classification and 3D refinement 3.3.3 Resolution estimation and Resmap calculation for the 70S P/P state maps 3.3.4 Model Validation 3.3.5 Resolution estimation for the Hibernating and Trans-translating maps 3.4 Structure of M. smegmatis 70S ribosome in P/P state 3.4.1 M. smegmatis small ribosomal subunit 3.4.2 M. smegmatis large ribosomal subunit 3.4.3 Species specific alteration in the 23S rRNA of the LSU in the M. smegmatis ribosome 3.4.4 Species specific alteration in r-proteins clustered near the functional sites of M. smegmatis ribosome 3.5 Structure of M. smegmatis 70S ribosome in the Hibernating state 3.5.1 Hibernation Promoting Factor 3.5.2 Structure of mRNA entry and exit sites of M. smegmatis 70S ribosome 3.6 Trans-Translating state of M. smegmatis 70S ribosome 3.6.1 Unique mechanism of tmRNA during trans-translation 4 Discussion 5 Conclusion 6 References 7 Appendix viii 8 Online access of cryo-EM maps and models 162 9 Author's publications related to this thesis during the

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Structural insights into species-specific features of the ribosome from the human pathogen Mycobacterium tuberculosis

Cited by 71 publications

References 75 publications

Selective translation by alternative bacterial ribosomes

Selective translation by alternative bacterial ribosomes

An overview of new antitubercular drugs, drug candidates, and their targets

Cryo-EM structure of the Mycobacterium smegmatis ribosome

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