Deciphering the Nucleotide and RNA Binding Selectivity of the Mayaro Virus Macro Domain.


Journal

Journal of molecular biology
ISSN: 1089-8638
Titre abrégé: J Mol Biol
Pays: Netherlands
ID NLM: 2985088R

Informations de publication

Date de publication:
31 05 2019
Historique:
received: 30 11 2018
revised: 01 03 2019
accepted: 08 04 2019
pubmed: 19 4 2019
medline: 24 3 2020
entrez: 19 4 2019
Statut: ppublish

Résumé

Mayaro virus (MAYV) is a member of Togaviridae family, which also includes Chikungunya virus as a notorious member. MAYV recently emerged in urban areas of the Americas, and this emergence emphasized the current paucity of knowledge about its replication cycle. The macro domain (MD) of MAYV belongs to the N-terminal region of its non-structural protein 3, part of the replication complex. Here, we report the first structural and dynamical characterization of a previously unexplored Alphavirus MD investigated through high-resolution NMR spectroscopy, along with data on its ligand selectivity and binding properties. The structural analysis of MAYV MD reveals a typical "macro" (ββαββαβαβα) fold for this polypeptide, while NMR-driven interaction studies provide in-depth insights into MAYV MD-ligand adducts. NMR data in concert with thermodynamics and biochemical studies provide convincing experimental evidence for preferential binding of adenosine diphosphate ribose (ADP-r) and adenine-rich RNAs to MAYV MD, thus shedding light on the structure-function relationship of a previously unexplored viral MD. The emerging differences with any other related MD are expected to enlighten distinct functions.

Identifiants

pubmed: 30998933
pii: S0022-2836(19)30207-4
doi: 10.1016/j.jmb.2019.04.013
pmc: PMC7094482
pii:
doi:

Substances chimiques

Nucleotides 0
Viral Nonstructural Proteins 0
Adenosine Diphosphate Ribose 20762-30-5
RNA 63231-63-0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2283-2297

Informations de copyright

Copyright © 2019 Elsevier Ltd. All rights reserved.

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Auteurs

Aikaterini C Tsika (AC)

Department of Pharmacy, University of Patras, GR-26504 Patras, Greece.

Efstathios Melekis (E)

Department of Pharmacy, University of Patras, GR-26504 Patras, Greece.

Sofia-Antigoni Tsatsouli (SA)

Department of Pharmacy, University of Patras, GR-26504 Patras, Greece.

Nicolas Papageorgiou (N)

AFMB, UMR7257 CNRS/Aix Marseille Université, Marseille, CEDEX 9, France.

Maria J Maté (MJ)

AFMB, UMR7257 CNRS/Aix Marseille Université, Marseille, CEDEX 9, France.

Bruno Canard (B)

AFMB, UMR7257 CNRS/Aix Marseille Université, Marseille, CEDEX 9, France.

Bruno Coutard (B)

UVE: Aix-Marseille Univ-IRD 190-Inserm 27-IHU Méditerranée Infection, Marseille, France. Electronic address: Bruno.Coutard@univ-amu.fr.

Detlef Bentrop (D)

Institute of Physiology II, Faculty of Medicine, University of Freiburg, D-79104 Freiburg, Germany.

Georgios A Spyroulias (GA)

Department of Pharmacy, University of Patras, GR-26504 Patras, Greece. Electronic address: G.A.Spyroulias@upatras.gr.

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