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Glycogen Synthase Kinase-3 Interaction Domain Enhances Phosphorylation of SARS-CoV-2 Nucleocapsid Protein.
Yun, Jun Seop; Song, Hyeeun; Kim, Nam Hee; Cha, So Young; Hwang, Kyu Ho; Lee, Jae Eun; Jeong, Cheol-Hee; Song, Sang Hyun; Kim, Seonghun; Cho, Eunae Sandra; Kim, Hyun Sil; Yook, Jong In.
  • Yun JS; Department of Oral Pathology, Yonsei University College of Dentistry, Seoul 03722, Korea.
  • Song H; These authors contributed equally to this work.
  • Kim NH; Department of Oral Pathology, Yonsei University College of Dentistry, Seoul 03722, Korea.
  • Cha SY; These authors contributed equally to this work.
  • Hwang KH; Department of Oral Pathology, Yonsei University College of Dentistry, Seoul 03722, Korea.
  • Lee JE; Department of Oral Pathology, Yonsei University College of Dentistry, Seoul 03722, Korea.
  • Jeong CH; Department of Oral Pathology, Yonsei University College of Dentistry, Seoul 03722, Korea.
  • Song SH; Department of Oral Pathology, Yonsei University College of Dentistry, Seoul 03722, Korea.
  • Kim S; Department of Oral Pathology, Yonsei University College of Dentistry, Seoul 03722, Korea.
  • Cho ES; Department of Oral Pathology, Yonsei University College of Dentistry, Seoul 03722, Korea.
  • Kim HS; Department of Oral Pathology, Yonsei University College of Dentistry, Seoul 03722, Korea.
  • Yook JI; Department of Oral Pathology, Yonsei University College of Dentistry, Seoul 03722, Korea.
Mol Cells ; 45(12): 911-922, 2022 Dec 31.
Article in English | MEDLINE | ID: covidwho-2203932
ABSTRACT
A structural protein of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), nucleocapsid (N) protein is phosphorylated by glycogen synthase kinase (GSK)-3 on the serine/arginine (SR) rich motif located in disordered regions. Although phosphorylation by GSK-3ß constitutes a critical event for viral replication, the molecular mechanism underlying N phosphorylation is not well understood. In this study, we found the putative alpha-helix L/FxxxL/AxxRL motif known as the GSK-3 interacting domain (GID), found in many endogenous GSK-3ß binding proteins, such as Axins, FRATs, WWOX, and GSKIP. Indeed, N interacts with GSK-3ß similarly to Axin, and Leu to Glu substitution of the GID abolished the interaction, with loss of N phosphorylation. The N phosphorylation is also required for its structural loading in a virus-like particle (VLP). Compared to other coronaviruses, N of Sarbecovirus lineage including bat RaTG13 harbors a CDK1-primed phosphorylation site and Gly-rich linker for enhanced phosphorylation by GSK-3ß. Furthermore, we found that the S202R mutant found in Delta and R203K/G204R mutant found in the Omicron variant allow increased abundance and hyper-phosphorylation of N. Our observations suggest that GID and mutations for increased phosphorylation in N may have contributed to the evolution of variants.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Nucleocapsid Proteins / Glycogen Synthase Kinase 3 / SARS-CoV-2 Type of study: Observational study / Prognostic study Topics: Variants Limits: Humans Language: English Journal: Mol Cells Journal subject: Molecular Biology Year: 2022 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Nucleocapsid Proteins / Glycogen Synthase Kinase 3 / SARS-CoV-2 Type of study: Observational study / Prognostic study Topics: Variants Limits: Humans Language: English Journal: Mol Cells Journal subject: Molecular Biology Year: 2022 Document Type: Article