4akl

Structure of the Crimean-Congo Haemorrhagic Fever Virus Nucleocapsid Protein

spinqualitylabelsall models 4akl, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4akl is a 2 chain structure with sequence from Cchfv. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: PGE Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed Crimean-Congo hemorrhagic fever virus (CCHFV) is an emerging tick-borne virus of the Bunyaviridae family responsible for fatal human disease for which preventative or therapeutic measures do not exist. We solved the crystal structure of the Baghdad-12 strain CCHFV nucleocapsid protein (N), a potential therapeutic target, at a resolution of 2.1 A. N comprises a large globular domain composed of both N- and C-terminal sequences, likely involved in RNA binding, and a protruding 'arm' domain with a conserved DEVD caspase-3 cleavage site at its apex. Alignment of our structure with that from the recently reported N from strain YL04057 shows close correspondence of all folds, but significant transposition of the arm through a rotation of 180 degrees and translation of 40 A. These observations suggest structural flexibility that may provide the basis for switching between alternative N protein conformations during important functions such as RNA binding or oligomerization. Our structure reveals surfaces likely involved in RNA binding and oligomerization, and functionally-critical residues within these domains were identified using a mini-genome system able to recapitulate CCHFV-specific RNA synthesis in cells. Caspase-3 cleaves the polypeptide chain at the exposed DEVD motif, however the cleaved N protein remains as an intact unit, likely due to the intimate association of N- and C-terminal fragments in the globular domain. Structural alignment with existing N proteins reveals that the closest CCHFV relative is not another bunyavirus, but instead the arenavirus Lassa virus, suggesting that current segmented negative strand RNA virus taxonomy may need revision. Structure, function and evolution of the Crimean-Congo hemorrhagic fever virus nucleocapsid protein.,Carter SD, Surtees R, Walter CT, Ariza A, Bergeron E, Nichol ST, Hiscox JA, Edwards TA, Barr JN J Virol. 2012 Aug 8. PMID:22875964 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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