4h5q
Crystal Structure of Rift Valley Fever Virus Nucleocapsid Protein Hexamer Bound to Single-stranded DNA
Structural highlights
FunctionNCAP_RVFV Encapsidates the genomic RNA, protecting it from nucleases (Probable) (PubMed:20547879). Displays high affinity for single-stranded nucleic acid (PubMed:23129612). The encapsidated genomic RNA is termed the nucleocapsid (NC) or ribonucleoprotein (PubMed:20547879). The ribonucleoprotein has a non-helical structure (PubMed:20547879). Serves as template for viral transcription and replication (By similarity). After replication, the nucleocapsid is recruited to the host Golgi apparatus by glycoprotein Gn for packaging into virus particles (By similarity).[UniProtKB:P21700][1] [2] [3] Publication Abstract from PubMedRift Valley fever and Toscana viruses are human pathogens for which no effective therapeutics exist. These and other phleboviruses have segmented negative-sense RNA genomes that are sequestered by a nucleocapsid protein (N) to form ribonucleoprotein (RNP) complexes of irregular, asymmetric structure, previously uncharacterized at high resolution. N binds nonspecifically to single-stranded RNA with nanomolar affinity. Crystal structures of Rift Valley fever virus N-RNA complexes reconstituted with defined RNAs of different length capture tetrameric, pentameric and hexameric N-RNA multimers. All N-N subunit contacts are mediated by a highly flexible alpha-helical arm. Arm movement gives rise to the three multimers in the crystal structures and also explains the asymmetric architecture of the RNP. Despite the flexible association of subunits, the crystal structures reveal an invariant, monomeric RNP building block, consisting of the core of one N subunit, the arm of a neighboring N, and four RNA nucleotides with the flanking phosphates. Up to three additional RNA nucleotides bind between subunits. The monomeric building block is matched in size to the repeating unit in viral RNP, as visualized by electron microscopy. N sequesters four RNA bases in a narrow hydrophobic binding slot and has polar contacts only with the sugar-phosphate backbone, which faces the solvent. All RNA bases, whether in the binding slot or in the subunit interface, face the protein in a manner that is incompatible with base pairing or with "reading" by the viral polymerase. Phleboviruses encapsidate their genomes by sequestering RNA bases.,Raymond DD, Piper ME, Gerrard SR, Skiniotis G, Smith JL Proc Natl Acad Sci U S A. 2012 Nov 5. PMID:23129612[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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