5F5O

Crystal structure of Marburg virus nucleoprotein core domain bound to VP35 regulation peptide

Summary for 5F5O

• Entry DOI: 10.2210/pdb5f5o/pdb
• Related: 5F5M
• Descriptor: Nucleoprotein, Peptide from Polymerase cofactor VP35, SULFATE ION, ... (4 entities in total)
• Functional Keywords: filovirus, marburg virus, nucleocapsid, nucleoprotein, complex, vp35 peptide, npbp, nuclear protein-peptide complex, nuclear protein/peptide
• Biological source: Lake Victoria marburgvirus (strain Ozolin-75) (MARV, Marburg virus (strain South Africa/Ozolin/1975)); More
• Cellular location: Virion: Q6UY69 Q6UY68
• Total number of polymer chains: 6
• Total formula weight: 135015.17

Authors

Guo, Y.,Liu, B.C.,Liu, X.,Li, G.B.,Wang, W.M.,Dong, S.S.,Wang, W.J. (deposition date: 2015-12-04, release date: 2017-05-31, Last modification date: 2024-03-20)

Primary citation

Liu, B.,Dong, S.,Li, G.,Wang, W.,Liu, X.,Wang, Y.,Yang, C.,Rao, Z.,Guo, Y.
Structural Insight into Nucleoprotein Conformation Change Chaperoned by VP35 Peptide in Marburg Virus
J. Virol., 91:-, 2017

PubMed Abstract: 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 NP, 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 NP C-terminal region, which shows high structural flexibility among filoviruses and may imply critical function during RNP formation. Moreover, the VP35 peptide-chaperoned NP 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. 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 NP 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.

PubMed: 28566377
DOI: 10.1128/JVI.00825-17

Experimental method

X-RAY DIFFRACTION (2.2 Å)