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Phase Separation of SARS-CoV-2 Nucleocapsid Protein with TDP-43 Is Dependent on C-Terminus Domains.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2024 Aug 12; Vol. 25 (16). Date of Electronic Publication: 2024 Aug 12. - Publication Year :
- 2024
-
Abstract
- The SARS-CoV-2 nucleocapsid protein (N protein) is critical in viral replication by undergoing liquid-liquid phase separation to seed the formation of a ribonucleoprotein (RNP) complex to drive viral genomic RNA (gRNA) translation and in suppressing both stress granules and processing bodies, which is postulated to increase uncoated gRNA availability. The N protein can also form biomolecular condensates with a broad range of host endogenous proteins including RNA binding proteins (RBPs). Amongst these RBPs are proteins that are associated with pathological, neuronal, and glial cytoplasmic inclusions across several adult-onset neurodegenerative disorders, including TAR DNA binding protein 43 kDa (TDP-43) which forms pathological inclusions in over 95% of amyotrophic lateral sclerosis cases. In this study, we demonstrate that the N protein can form biomolecular condensates with TDP-43 and that this is dependent on the N protein C-terminus domain (N-CTD) and the intrinsically disordered C-terminus domain of TDP-43. This process is markedly accelerated in the presence of RNA. In silico modeling suggests that the biomolecular condensate that forms in the presence of RNA is composed of an N protein quadriplex in which the intrinsically disordered TDP-43 C terminus domain is incorporated.
- Subjects :
- Humans
COVID-19 virology
COVID-19 metabolism
Protein Binding
Biomolecular Condensates metabolism
Biomolecular Condensates chemistry
RNA, Viral metabolism
RNA, Viral genetics
Phosphoproteins metabolism
Phosphoproteins chemistry
Phase Separation
DNA-Binding Proteins metabolism
DNA-Binding Proteins chemistry
SARS-CoV-2 metabolism
SARS-CoV-2 chemistry
Coronavirus Nucleocapsid Proteins metabolism
Coronavirus Nucleocapsid Proteins chemistry
Coronavirus Nucleocapsid Proteins genetics
Protein Domains
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 25
- Issue :
- 16
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 39201466
- Full Text :
- https://doi.org/10.3390/ijms25168779