Yun JS, Song H, Kim NH, Cha SY, Hwang KH, Lee JE, Jeong CH, Song SH, Kim S, Cho ES, Kim HS, Yook JI

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-3? constitutes a critical event for viral replication, the molecular mechanism underlying N phosphorylation is not ...

Read More

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-3? binding proteins, such as Axins, FRATs, WWOX, and GSKIP. Indeed, N interacts with GSK-3? 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-3?. 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.

Date: Dec. 31, 2022

View in: Pubmed Google Scholar

244904