tetano
Editor, Senior Moderator
Commun Biol
. 2022 Jul 16;5(1):711.
doi: 10.1038/s42003-022-03647-8.
Identification of a guanine-specific pocket in the protein N of SARS-CoV-2
J Rafael Ciges-Tomas[SUP] 1 2 [/SUP], María Luisa Franco[SUP] 3 [/SUP], Marçal Vilar[SUP] 4 [/SUP]
Affiliations
Abstract
The SARS-CoV-2 nucleocapsid protein (N) is responsible for RNA binding. Here we report the crystal structure of the C-terminal domain (N[SUP]CTD[/SUP]) in open and closed conformations and in complex with guanine triphosphate, GTP. The crystal structure and biochemical studies reveal a specific interaction between the guanine, a nucleotide enriched in the packaging signals regions of coronaviruses, and a highly conserved tryptophan residue (W330). In addition, EMSA assays with SARS-CoV-2 derived RNA hairpin loops from a putative viral packaging sequence showed the preference interaction of the N-CTD to RNA oligonucleotides containing G and the loss of the specificity in the mutant W330A. Here we propose that this interaction may facilitate the viral assembly process. In summary, we have identified a specific guanine-binding pocket in the N protein that may be used to design viral assembly inhibitors.
. 2022 Jul 16;5(1):711.
doi: 10.1038/s42003-022-03647-8.
Identification of a guanine-specific pocket in the protein N of SARS-CoV-2
J Rafael Ciges-Tomas[SUP] 1 2 [/SUP], María Luisa Franco[SUP] 3 [/SUP], Marçal Vilar[SUP] 4 [/SUP]
Affiliations
- PMID: 35842466
- DOI: 10.1038/s42003-022-03647-8
Abstract
The SARS-CoV-2 nucleocapsid protein (N) is responsible for RNA binding. Here we report the crystal structure of the C-terminal domain (N[SUP]CTD[/SUP]) in open and closed conformations and in complex with guanine triphosphate, GTP. The crystal structure and biochemical studies reveal a specific interaction between the guanine, a nucleotide enriched in the packaging signals regions of coronaviruses, and a highly conserved tryptophan residue (W330). In addition, EMSA assays with SARS-CoV-2 derived RNA hairpin loops from a putative viral packaging sequence showed the preference interaction of the N-CTD to RNA oligonucleotides containing G and the loss of the specificity in the mutant W330A. Here we propose that this interaction may facilitate the viral assembly process. In summary, we have identified a specific guanine-binding pocket in the N protein that may be used to design viral assembly inhibitors.