Characterization of SARS-CoV-2 nucleocapsid protein oligomers.

Autor: Farci D; Department of Plant Physiology, Institute of Biology, Warsaw University of Life Sciences - SGGW, Warsaw, Poland; Department of Chemistry, Umeå University, Umeå, Sweden; Laboratory of Plant Physiology and Photobiology, Department of Life and Environmental Sciences, University of Cagliari, Cagliari, Italy; ReGenFix Laboratories, R&D Department, Sardara, Italy. Electronic address: domenica.farci@unica.it., Graça AT; Department of Chemistry, Umeå University, Umeå, Sweden., Hall M; Department of Chemistry, Umeå University, Umeå, Sweden., Haniewicz P; Department of Plant Physiology, Institute of Biology, Warsaw University of Life Sciences - SGGW, Warsaw, Poland., Kereïche S; Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague, Czech Republic., Faull P; The Francis Crick Institute, London, United Kingdom; Proteomics Facility, University of Texas at Austin, Austin, USA., Kirkpatrick J; The Francis Crick Institute, London, United Kingdom., Tramontano E; Laboratory of Molecular Virology, Department of Life and Environmental Sciences, University of Cagliari, Cagliari, Italy., Schröder WP; Department of Chemistry, Umeå University, Umeå, Sweden., Piano D; Department of Plant Physiology, Institute of Biology, Warsaw University of Life Sciences - SGGW, Warsaw, Poland; Laboratory of Plant Physiology and Photobiology, Department of Life and Environmental Sciences, University of Cagliari, Cagliari, Italy; ReGenFix Laboratories, R&D Department, Sardara, Italy. Electronic address: dario.piano@unica.it.
Jazyk: angličtina
Zdroj: Journal of structural biology [J Struct Biol] 2024 Dec 13; Vol. 217 (1), pp. 108162. Date of Electronic Publication: 2024 Dec 13.
DOI: 10.1016/j.jsb.2024.108162
Abstrakt: Oligomers of the SARS-CoV-2 nucleocapsid (N) protein are characterized by pronounced instability resulting in fast degradation. This property likely relates to two contrasting behaviors of the N protein: genome stabilization through a compact nucleocapsid during cell evasion and genome release by nucleocapsid disassembling during infection. In vivo, the N protein forms rounded complexes of high molecular mass from its interaction with the viral genome. To study the N protein and understand its instability, we analyzed degradation profiles under different conditions by size-exclusion chromatography and characterized samples by mass spectrometry and cryo-electron microscopy. We identified self-cleavage properties of the N protein based on specific Proprotein convertases activities, with Cl - playing a key role in modulating stability and degradation. These findings allowed isolation of a stable oligomeric complex of N, for which we report the 3D structure at ∼6.8 Å resolution. Findings are discussed considering available knowledge about the coronaviruses' infection cycle.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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