Stringent control of the RNA-dependent RNA polymerase translocation revealed by multiple intermediate structures
| Autor: | Han-Qing Ye, Xuping Jing, Meihua Wang, Bo Shu, Rui Li, Peng Gong |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Models Molecular Transcription Elongation Genetic Genes Viral Catalytic complex Protein Conformation viruses Science Amino Acid Motifs General Physics and Astronomy RNA-dependent RNA polymerase Biological Transport Active Crystallography X-Ray General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences chemistry.chemical_compound Viral Proteins 0302 clinical medicine RNA polymerase Virology Catalytic Domain Humans 030212 general & internal medicine Amino Acid Sequence lcsh:Science Gene Polymerase X-ray crystallography Multidisciplinary biology Base Sequence Chemistry RNA General Chemistry RNA-Dependent RNA Polymerase Enterovirus A Human 030104 developmental biology Amino Acid Substitution Coding strand Enzyme mechanisms Nucleic acid biology.protein Biophysics Mutagenesis Site-Directed Nucleic Acid Conformation RNA Viral lcsh:Q |
| Zdroj: | Nature Communications Nature Communications, Vol 11, Iss 1, Pp 1-11 (2020) |
| ISSN: | 2041-1723 |
| Popis: | Each polymerase nucleotide addition cycle is associated with two primary conformational changes of the catalytic complex: the pre-chemistry active site closure and post-chemistry translocation. While active site closure is well interpreted by numerous crystallographic snapshots, translocation intermediates are rarely captured. Here we report three types of intermediate structures in an RNA-dependent RNA polymerase (RdRP). The first two types, captured in forward and reverse translocation events, both highlight the role of RdRP-unique motif G in restricting the RNA template movement, corresponding to the rate-limiting step in translocation. By mutating two critical residues in motif G, we obtain the third type of intermediates that may mimic the transition state of this rate-limiting step, demonstrating a previously unidentified movement of the template strand. We propose that a similar strategy may be utilized by other classes of nucleic acid polymerases to ensure templating nucleotide positioning for efficient catalysis through restricting interactions with template RNA. During translocation by viral RNA-dependent RNA polymerases (RdRP), the template-product RNA duplex moves in an asymmetric manner. Here the authors describe several crystal structures of RdRP translocations intermediates that, along with enzymological data, provide a comprehensive view of RdRP translocation. |
| Databáze: | OpenAIRE |
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