Structural basis for ribosome protein S1 interaction with RNA in trans -translation of Mycobacterium tuberculosis
| Autor: | Huilin Wang, Yazhuang Dai, Xinli Liao, Meijing Hou, Hongwei Yao, Yi Fan, Donghai Lin, Chenyun Guo |
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| Rok vydání: | 2017 |
| Předmět: |
Ribosomal Proteins
0301 basic medicine Protein Conformation Biophysics Biology Biochemistry Ribosome Structure-Activity Relationship 03 medical and health sciences Ribosomal protein 30S Binding site Molecular Biology Binding Sites 030102 biochemistry & molecular biology RNA Translation (biology) Mycobacterium tuberculosis Cell Biology Molecular Docking Simulation S1 domain RNA Bacterial 030104 developmental biology Models Chemical Protein Biosynthesis Trans-translation Protein Binding |
| Zdroj: | Biochemical and Biophysical Research Communications. 487:268-273 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2017.04.048 |
| Popis: | Ribosomal protein S1 (RpsA), the largest 30S protein in ribosome, plays a significant role in translation and trans-translation. In Mycobacterium tuberculosis, the C-terminus of RpsA is known as tuberculosis drug target of pyrazinoic acid, which inhibits the interaction between MtRpsA and tmRNA in trans-translation. However, the molecular mechanism underlying the interaction of MtRpsA with tmRNA remains unknown. We herein analyzed the interaction of the C-terminal domain of MtRpsA with three RNA fragments poly(A), sMLD and pre-sMLD. NMR titration analysis revealed that the RNA binding sites on MtRpsACTD are mainly located in the β2, β3 and β5 strands and the adjacent L3 loop of the S1 domain. Fluorescence experiments determined the MtRpsACTD binding to RNAs are in the micromolar affinity range. Sequence analysis also revealed conserved residues in the mapped RNA binding region. Residues L304, V305, G308, F310, H322, I323, R357 and I358 were verified to be the key residues influencing the interaction between MtRpsACTD and pre-sMLD. Molecular docking further confirmed that the poly(A)-like sequence and sMLD of tmRNA are all involved in the protein-RNA interaction, through charged interaction and hydrogen bonds. The results will be beneficial for designing new anti-tuberculosis drugs. |
| Databáze: | OpenAIRE |
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