Copper(II) coordination to the intrinsically disordered region of SARS-CoV-2 Nsp1.
Maryann MoralesMoon Young YangWilliam A Goddard IiiHarry B GrayJay R WinklerPublished in: Proceedings of the National Academy of Sciences of the United States of America (2024)
The intrinsically disordered C-terminal peptide region of severe acute respiratory syndrome coronavirus 2 nonstructural protein-1 (Nsp1-CT) inhibits host protein synthesis by blocking messenger RNA (mRNA) access to the 40S ribosome entrance tunnel. Aqueous copper(II) ions bind to the disordered peptide with micromolar affinity, creating a possible strategy to restore protein synthesis during host infection. Electron paramagnetic resonance (EPR) and tryptophan fluorescence measurements on a 10-residue model of the disordered protein region (Nsp1-CT 10 ), combined with advanced quantum mechanics calculations, suggest that the peptide binds to copper(II) as a multidentate ligand. Two optimized computational models of the copper(II)-peptide complexes were derived: One corresponding to pH 6.5 and the other describing the complex at pH 7.5 to 8.5. Simulated EPR spectra based on the calculated model structures are in good agreement with experimental spectra.
Keyphrases
- sars cov
- respiratory syndrome coronavirus
- density functional theory
- energy transfer
- computed tomography
- oxide nanoparticles
- molecular dynamics
- image quality
- binding protein
- dual energy
- coronavirus disease
- amino acid
- protein protein
- high resolution
- magnetic resonance imaging
- ionic liquid
- mass spectrometry
- small molecule
- water soluble