Crystal Structure of the Dengue Virus Methyltransferase Bound to a 5′-Capped Octameric RNA
| Autor: | Julien Lescar, Christian G. Noble, Li Jian Yap, Christophe Bodenreider, Siew Pheng Lim, Ka Yan Chung, Pei Yong Shi, Dahai Luo |
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| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Models
Molecular RNA Caps Base pair Stereochemistry Science Protein domain Molecular Sequence Data RNA-binding protein Biology Crystallography X-Ray Viral Proteins Protein structure Biochemistry/RNA Structure Amino Acid Sequence Nucleic acid structure Multidisciplinary Binding Sites RNA Methyltransferases Dengue Virus Molecular biology Protein Structure Tertiary Virology/Viral Replication and Gene Regulation Guanylyltransferase activity Transfer RNA Medicine Nucleic Acid Conformation RNA Viral Biochemistry/Transcription and Translation Research Article Protein Binding |
| Zdroj: | PLoS ONE PLoS ONE, Vol 5, Iss 9 (2010) |
| ISSN: | 1932-6203 |
| Popis: | The N-terminal domain of the flavivirus NS5 protein functions as a methyltransferase (MTase). It sequentially methylates the N7 and 2'-O positions of the viral RNA cap structure (GpppA→(7me)GpppA→(7me)GpppA(2'-O-me)). The same NS5 domain could also have a guanylyltransferase activity (GTP+ppA-RNA→GpppA). The mechanism by which this protein domain catalyzes these three distinct functions is currently unknown. Here we report the crystallographic structure of DENV-3 MTase in complex with a 5'-capped RNA octamer (G(ppp)AGAACCUG) at a resolution of 2.9 A. Two RNA octamers arranged as kissing loops are encircled by four MTase monomers around a 2-fold non-crystallography symmetry axis. Only two of the four monomers make direct contact with the 5' end of RNA. The RNA structure is stabilised by the formation of several intra and intermolecular base stacking and non-canonical base pairs. The structure may represent the product of guanylylation of the viral genome prior to the subsequent methylation events that require repositioning of the RNA substrate to reach to the methyl-donor sites. The crystal structure provides a structural explanation for the observed trans-complementation of MTases with different methylation defects. |
| Databáze: | OpenAIRE |
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