2XBM

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

2XBM の概要

• エントリーDOI: 10.2210/pdb2xbm/pdb
• 分子名称: NONSTRUCTURAL PROTEIN NS5, 5'-(*G3AP*GP*AP*AP*CP*CP*UP*GP*A)-3', SULFATE ION, ... (6 entities in total)
• 機能のキーワード: flavivirus, rna binding protein
• 由来する生物種: DENGUE VIRUS
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 128667.67

構造登録者

Yap, L.J.,Luo, D.H.,Chung, K.Y.,Lim, S.P.,Bodenreider, C.,Noble, C.,Shi, P.Y.,Lescar, J. (登録日: 2010-04-13, 公開日: 2010-09-29, 最終更新日: 2025-12-10)

主引用文献

Yap, L.J.,Luo, D.H.,Chung, K.Y.,Lim, S.P.,Bodenreider, C.,Noble, C.,Shi, P.Y.,Lescar, J.
Crystal Structure of the Dengue Virus Methyltransferase Bound to a 5'-Capped Octameric RNA
Plos One, 5:12836-, 2010

PubMed Abstract: 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.

PubMed: 20862256
DOI: 10.1371/JOURNAL.PONE.0012836

実験手法

X-RAY DIFFRACTION (2.9 Å)