Dengue virus nonstructural protein 5 adopts multiple conformations in solution

Cécile Bussetta, Kyung Choi

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Dengue virus (DENV) nonstructural protein 5 (NS5) is composed of two globular domains separated by a 10-residue linker. The N-terminal domain participates in the synthesis of a mRNA cap 1 structure ( 7MeGpppA2′OMe) at the 5′ end of the viral genome and possesses guanylyltransferase, guanine-N7-methyltransferase, and nucleoside-2′O-methyltransferase activities. The C-terminal domain is an RNA-dependent RNA polymerase responsible for viral RNA synthesis. Although crystal structures of the two isolated domains have been obtained, there are no structural data for full-length NS5. It is also unclear whether the two NS5 domains interact with each other to form a stable structure in which the relative orientation of the two domains is fixed. To investigate the structure and dynamics of DENV type 3 NS5 in solution, we conducted small-angle X-ray scattering experiments with the full-length protein. NS5 was found to be monomeric and well-folded under the conditions tested. The results of these experiments also suggest that NS5 adopts multiple conformations in solution, ranging from compact to more extended forms in which the two domains do not seem to interact with each other. We interpret the multiple conformations of NS5 observed in solution as resulting from weak interactions between the two NS5 domains and flexibility of the linker in the absence of other components of the replication complex.

Original languageEnglish (US)
Pages (from-to)5921-5931
Number of pages11
JournalBiochemistry
Volume51
Issue number30
DOIs
StatePublished - Jul 31 2012

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Dengue Virus
Viruses
Conformations
Proteins
Methyltransferases
RNA Replicase
Protein Conformation
Viral Genome
Viral RNA
Guanine
Nucleosides
X-Rays
X ray scattering
Messenger RNA
Genes
Crystal structure
Experiments

ASJC Scopus subject areas

  • Biochemistry

Cite this

Dengue virus nonstructural protein 5 adopts multiple conformations in solution. / Bussetta, Cécile; Choi, Kyung.

In: Biochemistry, Vol. 51, No. 30, 31.07.2012, p. 5921-5931.

Research output: Contribution to journalArticle

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