A core network in the SARS-CoV-2 nucleocapsid NTD mediates structural integrity and selective RNA-binding

Area of Science:

• Virology
• Structural Biology
• Molecular Biology

Background:

• The SARS-CoV-2 nucleocapsid protein (N) is vital for viral RNA genome processing.
• The N-terminal domain (NTD) of the nucleocapsid protein is implicated in specific RNA interactions, but high-resolution structures are limited.
• The precise mechanism of NTD-RNA complex formation and the impact of emerging mutations remain unclear.

Purpose of the Study:

• To investigate the structural integrity and RNA-binding properties of the SARS-CoV-2 nucleocapsid protein NTD.
• To elucidate the molecular impact of NTD mutations on protein stability and RNA interactions.
• To understand the role of conserved residues in NTD function and evolution.

Main Methods:

• X-ray crystallography
• Solution Nuclear Magnetic Resonance (NMR) spectroscopy
• Structural analysis of NTD mutations

Main Results:

• A core network of conserved residues is essential for NTD structural integrity and RNA binding.
• This network facilitates communication between flexible loop regions involved in RNA recognition.
• Mutations within this core network significantly affect protein stability and RNA-binding capabilities.

Conclusions:

• The conserved core residue network is critical for the stability and plasticity of the nucleocapsid NTD.
• This network underpins the protein's selective RNA interactions and versatile RNA processing roles.
• The findings provide insights into the evolutionary robustness of the nucleocapsid NTD in Betacoronaviruses.