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

Aikaterini C Tsika1, Efstathios Melekis1, Sofia-Antigoni Tsatsouli1

  • 1Department of Pharmacy, University of Patras, GR-26504 Patras, Greece.

Journal of Molecular Biology
|April 19, 2019
PubMed

Insights

Mayaro virus macro domain (MD) structure was determined using NMR. This study reveals its preferential binding to adenosine diphosphate ribose and adenine-rich RNAs, offering insights into viral replication.

Area of Science:

  • Virology
  • Structural Biology
  • Molecular Biology

Background:

  • Mayaro virus (MAYV), a Togaviridae family member, has recently emerged in the Americas.
  • Knowledge regarding MAYV's replication cycle is limited, particularly concerning its non-structural protein 3 (nsP3) macro domain (MD).
  • The nsP3 protein is crucial for the viral replication complex.

Purpose of the Study:

  • To perform the first structural and dynamical characterization of the MAYV nsP3 macro domain (MD).
  • To investigate the ligand selectivity and binding properties of the MAYV MD.
  • To elucidate the structure-function relationship of this unexplored viral MD.

Main Methods:

  • High-resolution Nuclear Magnetic Resonance (NMR) spectroscopy was employed for structural and dynamical characterization.
  • Ligand interaction studies were conducted using NMR-driven techniques.
  • Thermodynamic and biochemical assays were integrated with NMR data.

Main Results:

  • The MAYV MD exhibits a typical 'macro' fold (ββαββαβαβα).
  • NMR studies revealed preferential binding of adenosine diphosphate ribose (ADP-r) and adenine-rich RNAs to the MAYV MD.
  • Interaction studies provided in-depth insights into MAYV MD-ligand adducts.

Conclusions:

  • The study provides the first structural and binding data for the MAYV MD.
  • Preferential binding to ADP-r and adenine-rich RNAs suggests a role in viral replication.
  • Observed differences compared to other MDs may indicate distinct functional roles, aiding in understanding MAYV pathogenesis.
Keywords:
ADP-riboseAlphavirusMayaro virusRNAmacro domain

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