Version 1
: Received: 3 July 2024 / Approved: 4 July 2024 / Online: 4 July 2024 (08:32:20 CEST)
How to cite:
Strong, M. J.; McLellan, C.; Kalpanis, B.; Droppelmann, C. A.; Junop, M. Phase separation of SARS-CoV-2 nucleocapsid protein with TDP-43 is dependant on C-terminus domains. Preprints2024, 2024070408. https://doi.org/10.20944/preprints202407.0408.v1
Strong, M. J.; McLellan, C.; Kalpanis, B.; Droppelmann, C. A.; Junop, M. Phase separation of SARS-CoV-2 nucleocapsid protein with TDP-43 is dependant on C-terminus domains. Preprints 2024, 2024070408. https://doi.org/10.20944/preprints202407.0408.v1
Strong, M. J.; McLellan, C.; Kalpanis, B.; Droppelmann, C. A.; Junop, M. Phase separation of SARS-CoV-2 nucleocapsid protein with TDP-43 is dependant on C-terminus domains. Preprints2024, 2024070408. https://doi.org/10.20944/preprints202407.0408.v1
APA Style
Strong, M. J., McLellan, C., Kalpanis, B., Droppelmann, C. A., & Junop, M. (2024). Phase separation of SARS-CoV-2 nucleocapsid protein with TDP-43 is dependant on C-terminus domains. Preprints. https://doi.org/10.20944/preprints202407.0408.v1
Chicago/Turabian Style
Strong, M. J., Cristian A Droppelmann and Murray Junop. 2024 "Phase separation of SARS-CoV-2 nucleocapsid protein with TDP-43 is dependant on C-terminus domains" Preprints. https://doi.org/10.20944/preprints202407.0408.v1
Abstract
The SARS-CoV-2 nucleocapsid protein (N protein) is critical to 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 also 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 dependant 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 modelling suggests that the biomolecular condensate that formed in the presence of RNA is composed of a N protein quadriplex in which the intrinsically disordered TDP-43 C terminus domain is incorporated.
Medicine and Pharmacology, Neuroscience and Neurology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
