8xab

Crystal structure of Ubl1 domain of nonstructural protein 3 of SARS-CoV-2

spinqualitylabelsall models 8xab, resolution 1.49Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8xab is a 1 chain structure with sequence from Severe acute respiratory syndrome coronavirus 2. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.49Å Ligands: GOL Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed The connection between SARS-CoV-2 replication-transcription complexes (RTCs) and nucleocapsid (N) protein is critical for regulating genomic RNA replication and virion packaging over the viral life cycle. However, the mechanism that dynamically regulates genomic RNA packaging and replication remains elusive. Here, we demonstrate that the N-terminal domain (NTD) of SARS-CoV-2 nonstructural protein 3 (Nsp3), a core component of viral RTCs, binds N protein and displaces RNA in a concentration-dependent manner. This interaction disrupts liquid-liquid phase separation of N protein driven by N protein-RNA interactions which is crucial for virion packaging and viral replication. We also report a high-resolution crystal structure of the Nsp3 ubiquitin-like domain 1 (Ubl1) at 1.49 A, which reveals abundant negative charges on the protein surface. Sequence and structural analyses identify several conserved motifs at the Ubl1-N protein interface and a previously unexplored highly negative groove, providing insights into the molecular mechanism of Ubl1-mediated modulation of N protein-RNA binding. Our findings elucidate the mechanism of dynamic regulation of SARS-CoV-2 genomic RNA replication and packaging over the viral life cycle. Targeting the conserved Ubl1-N protein interaction hotspots also promises to aid in the development of broad-spectrum antivirals against pathogenic coronaviruses. N-terminus of SARS-CoV-2 nonstructural protein 3 interrupts RNA-driven phase separation of N protein by displacing RNA.,Ke Z, Zhang H, Wang Y, Wang J, Peng F, Wang J, Liu X, Hu H, Li Y J Biol Chem. 2024 Sep 26:107828. doi: 10.1016/j.jbc.2024.107828. PMID:39341499 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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