9EWH

SARS-CoV-2 Nucleocapsid N-terminal domain (NTD) mutant Y109A

Summary for 9EWH

• Entry DOI: 10.2210/pdb9ewh/pdb
• Related: 9EVY 9EXB 9EZB 9F5J 9F5L 9F7A 9F7C 9F83 9FBG
• Descriptor: Nucleoprotein (2 entities in total)
• Functional Keywords: sars-cov-2, nucelocapsid, n-terminal domain, viral protein
• Biological source: Severe acute respiratory syndrome coronavirus 2
• Total number of polymer chains: 4
• Total formula weight: 59209.97

Authors

Dhamotharan, K.,Schlundt, A.,Guenther, S. (deposition date: 2024-04-03, release date: 2024-11-20, Last modification date: 2024-12-18)

Primary citation

Dhamotharan, K.,Korn, S.M.,Wacker, A.,Becker, M.A.,Gunther, S.,Schwalbe, H.,Schlundt, A.
A core network in the SARS-CoV-2 nucleocapsid NTD mediates structural integrity and selective RNA-binding.
Nat Commun, 15:10656-10656, 2024

PubMed Abstract: The SARS-CoV-2 nucleocapsid protein is indispensable for viral RNA genome processing. Although the N-terminal domain (NTD) is suggested to mediate specific RNA-interactions, high-resolution structures with viral RNA are still lacking. Available hybrid structures of the NTD with ssRNA and dsRNA provide valuable insights; however, the precise mechanism of complex formation remains elusive. Similarly, the molecular impact of nucleocapsid NTD mutations that have emerged since 2019 has not yet been fully explored. Using crystallography and solution NMR, we investigate how NTD mutations influence structural integrity and RNA-binding. We find that both features rely on a core network of residues conserved in Betacoronaviruses, crucial for protein stability and communication among flexible loop-regions that facilitate RNA-recognition. Our comprehensive structural analysis demonstrates that contacts within this network guide selective RNA-interactions. We propose that the core network renders the NTD evolutionarily robust in stability and plasticity for its versatile RNA processing roles.

PubMed: 39653699
DOI: 10.1038/s41467-024-55024-0

Experimental method

X-RAY DIFFRACTION (1.93 Å)