Crystal structure of the dengue virus methyltransferase bound to a 5'-capped octameric RNA.

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+...

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Autores principales:	Li Jian Yap, Dahai Luo, Ka Yan Chung, Siew Pheng Lim, Christophe Bodenreider, Christian Noble, Pei-Yong Shi, Julien Lescar
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b42b0853a571424f90c622a09a1b7d53
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spelling	oai:doaj.org-article:b42b0853a571424f90c622a09a1b7d532021-11-18T06:35:04ZCrystal structure of the dengue virus methyltransferase bound to a 5'-capped octameric RNA.1932-620310.1371/journal.pone.0012836https://doaj.org/article/b42b0853a571424f90c622a09a1b7d532010-09-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20862256/?tool=EBIhttps://doaj.org/toc/1932-6203The 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.Li Jian YapDahai LuoKa Yan ChungSiew Pheng LimChristophe BodenreiderChristian NoblePei-Yong ShiJulien LescarPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 9 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Li Jian Yap Dahai Luo Ka Yan Chung Siew Pheng Lim Christophe Bodenreider Christian Noble Pei-Yong Shi Julien Lescar Crystal structure of the dengue virus methyltransferase bound to a 5'-capped octameric RNA.
description	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.
format	article
author	Li Jian Yap Dahai Luo Ka Yan Chung Siew Pheng Lim Christophe Bodenreider Christian Noble Pei-Yong Shi Julien Lescar
author_facet	Li Jian Yap Dahai Luo Ka Yan Chung Siew Pheng Lim Christophe Bodenreider Christian Noble Pei-Yong Shi Julien Lescar
author_sort	Li Jian Yap
title	Crystal structure of the dengue virus methyltransferase bound to a 5'-capped octameric RNA.
title_short	Crystal structure of the dengue virus methyltransferase bound to a 5'-capped octameric RNA.
title_full	Crystal structure of the dengue virus methyltransferase bound to a 5'-capped octameric RNA.
title_fullStr	Crystal structure of the dengue virus methyltransferase bound to a 5'-capped octameric RNA.
title_full_unstemmed	Crystal structure of the dengue virus methyltransferase bound to a 5'-capped octameric RNA.
title_sort	crystal structure of the dengue virus methyltransferase bound to a 5'-capped octameric rna.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/b42b0853a571424f90c622a09a1b7d53
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Crystal structure of the dengue virus methyltransferase bound to a 5'-capped octameric RNA.

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