Identification of a guanine-specific pocket in the protein N of SARS-CoV-2
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Identification of a guanine-specific pocket in the protein N of SARS-CoV-2. / Rafael Ciges-Tomas, J.; Franco, María Luisa; Vilar, Marçal.
In: Communications Biology , Vol. 5, No. 1, 711, 2022.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Identification of a guanine-specific pocket in the protein N of SARS-CoV-2
AU - Rafael Ciges-Tomas, J.
AU - Franco, María Luisa
AU - Vilar, Marçal
N1 - © 2022. The Author(s).
PY - 2022
Y1 - 2022
N2 - The SARS-CoV-2 nucleocapsid protein (N) is responsible for RNA binding. Here we report the crystal structure of the C-terminal domain (NCTD) 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.
AB - The SARS-CoV-2 nucleocapsid protein (N) is responsible for RNA binding. Here we report the crystal structure of the C-terminal domain (NCTD) 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.
KW - COVID-19
KW - Guanine
KW - Humans
KW - Nucleocapsid Proteins/chemistry
KW - RNA, Viral/metabolism
KW - SARS-CoV-2/genetics
U2 - 10.1038/s42003-022-03647-8
DO - 10.1038/s42003-022-03647-8
M3 - Journal article
C2 - 35842466
VL - 5
JO - Communications Biology
JF - Communications Biology
SN - 2399-3642
IS - 1
M1 - 711
ER -
ID: 314626731