Structural highlights
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). [VP35_MABVO] Acts as a polymerase cofactor in the RNA polymerase transcription and replication complex.
Publication Abstract from PubMed
Filovirus nucleoprotein (NP), viral protein 35 (VP35), and polymerase L are essential for viral replication and nucleocapsid formation. Here, we identify a 28-residue peptide (NP binding peptide [NPBP]) from Marburg virus (MARV) VP35 through sequence alignment with previously identified Ebola virus (EBOV) NPBP, which bound to the core region (residues 18 to 344) of the N-terminal portion of MARV NP with high affinity. The crystal structure of the MARV NP core/NPBP complex at a resolution of 2.6 A revealed that NPBP binds to the C-terminal region of the NP core via electrostatic and nonpolar interactions. Further structural analysis revealed that the MARV and EBOV NP cores hold a conserved binding pocket for NPBP, and this pocket could serve as a promising target for the design of universal drugs against filovirus infection. In addition, cross-binding assays confirmed that the NP core of MARV or EBOV can bind the NPBP from the other virus, although with moderately reduced binding affinities that result from termini that are distinct between the MARV and EBOV NPBPs.IMPORTANCE Historically, Marburg virus (MARV) has caused severe disease with up to 90% lethality. Among the viral proteins produced by MARV, NP and VP35 are both multifunctional proteins that are essential for viral replication. In its relative, Ebola virus (EBOV), an N-terminal peptide from VP35 binds to the NP N-terminal region with high affinity. Whether this is a common mechanism among filoviruses is an unsolved question. Here, we present the crystal structure of a complex that consists of the core domain of MARV NP and the NPBP peptide from VP35. As we compared MARV NPBP with EBOV NPBP, several different features at the termini were identified. Although these differences reduce the affinity of the NP core for NPBPs across genera, a conserved pocket in the C-terminal region of the NP core makes cross-species binding possible. Our results expand our knowledge of filovirus NP-VP35 interactions and provide more details for therapeutic intervention.
Crystal Structure of the Marburg Virus Nucleoprotein Core Domain Chaperoned by a VP35 Peptide Reveals a Conserved Drug Target for Filovirus.,Zhu T, Song H, Peng R, Shi Y, Qi J, Gao GF J Virol. 2017 Aug 24;91(18). pii: e00996-17. doi: 10.1128/JVI.00996-17. Print, 2017 Sep 15. PMID:28659479[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Zhu T, Song H, Peng R, Shi Y, Qi J, Gao GF. Crystal Structure of the Marburg Virus Nucleoprotein Core Domain Chaperoned by a VP35 Peptide Reveals a Conserved Drug Target for Filovirus. J Virol. 2017 Aug 24;91(18). pii: e00996-17. doi: 10.1128/JVI.00996-17. Print, 2017 Sep 15. PMID:28659479 doi:http://dx.doi.org/10.1128/JVI.00996-17
