5f5m

Crystal structure of Marburg virus nucleoprotein core domain

spinqualitylabelsall models 5f5m, resolution 2.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5f5m is a 2 chain structure with sequence from Lake victoria marburgvirus (strain ozolin-75). Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Related: 5f5o Gene: NP (Lake Victoria marburgvirus (strain Ozolin-75)) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [NCAP_MABVO] Encapsidates the genome, protecting it from nucleases. The encapsidated genomic RNA is termed the nucleocapsid and serves as template for transcription and replication. During replication, encapsidation by NP is coupled to RNA synthesis and all replicative products are resistant to nucleases (By similarity). Publication Abstract from PubMed Marburg virus (MARV) encodes a nucleoprotein (NP) to encapsidate its genome by oligomerization and form a ribonucleoprotein complex (RNP). According to previous investigation on nonsegmented negative-sense RNA viruses (nsNSV), the newly synthesized NPs must be prevented from indiscriminately binding to noncognate RNAs. During the viral RNA synthesis process, the RNPs undergo a transition from an RNA-bound form to a template-free form, to open access for the interaction between the viral polymerase and the RNA template. In filoviruses, this transition is regulated by VP35 peptide and other viral components. To further understand the dynamic process of filovirus RNP formation, we report here the structure of MARV NPcore, both in the apo form and in the VP35 peptide-chaperoned form. These structures reveal a typical bilobed structure, with a positive-charged RNA binding groove between two lobes. In the apo form, the MARV NP exists in an interesting hexameric state formed by the hydrophobic interaction within the long helix of the NPcore C-terminal region, which shows high structural flexibility among filoviruses and may imply critical function during RNP formation. Moreover, the VP35 peptide-chaperoned NPcore remains in a monomeric state and completely loses its affinity for single-stranded RNA (ssRNA). The structural comparison reveals that the RNA binding groove undergoes a transition from closed state to open state, chaperoned by VP35 peptide, thus preventing the interaction for viral RNA. Our investigation provides considerable structural insight into the filovirus RNP working mechanism and may support the development of antiviral therapies targeting the RNP formation of filovirus.IMPORTANCE Marburg virus is one of the most dangerous viruses, with high morbidity and mortality. A recent outbreak in Angola in 2005 caused the deaths of 272 persons. NP is one of the most essential proteins, as it encapsidates and protects the whole virus genome simultaneously with self-assembly oligomerization. Here we report the structures of MARV NPcore in two different forms. In the MARV NP apo form, we identify an interesting hexamer formed by hydrophobic interaction within a long helix, which is highly conserved and flexible among filoviruses and may indicate its critical function during the virus RNP formation. Moreover, the structural comparison with the NP-VP35 peptide complex reveals a structural transition chaperoned by VP35, in which the RNA binding groove undergoes a transition from closed state to open state. Finally, we discussed the high conservation and critical role of the VP35 binding pocket and its potential use for therapeutic development. Structural Insight into Nucleoprotein Conformation Change Chaperoned by VP35 Peptide in Marburg Virus.,Liu B, Dong S, Li G, Wang W, Liu X, Wang Y, Yang C, Rao Z, Guo Y J Virol. 2017 Jul 27;91(16). pii: e00825-17. doi: 10.1128/JVI.00825-17. Print, 2017 Aug 15. PMID:28566377 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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