5t3w
Marburg virus VP30 bound to nucleoprotein
Structural highlights
FunctionNCAP_MABVM 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).VP30_MABVM Acts as a transcription anti-termination factor immediately after transcription initiation, but does not affect transcription elongation. This function has been found to be dependent on the formation of an RNA secondary structure at the transcription start site of the first gene (By similarity). Publication Abstract from PubMedFiloviruses are capable of causing deadly hemorrhagic fevers. All nonsegmented negative-sense RNA-virus nucleocapsids are composed of a nucleoprotein (NP), a phosphoprotein (VP35) and a polymerase (L). However, the VP30 RNA-synthesis co-factor is unique to the filoviruses. The assembly, structure, and function of the filovirus RNA replication complex remain unclear. Here, we have characterized the interactions of Ebola, Sudan and Marburg virus VP30 with NP using in vitro biochemistry, structural biology and cell-based mini-replicon assays. We have found that the VP30 C-terminal domain interacts with a short peptide in the C-terminal region of NP. Further, we have solved crystal structures of the VP30-NP complex for both Ebola and Marburg viruses. These structures reveal that a conserved, proline-rich NP peptide binds a shallow hydrophobic cleft on the VP30 C-terminal domain. Structure-guided Ebola virus VP30 mutants have altered affinities for the NP peptide. Correlation of these VP30-NP affinities with the activity for each of these mutants in a cell-based mini-replicon assay suggests that the VP30-NP interaction plays both essential and inhibitory roles in Ebola virus RNA synthesis. The Ebola Virus VP30-NP Interaction Is a Regulator of Viral RNA Synthesis.,Kirchdoerfer RN, Moyer CL, Abelson DM, Saphire EO PLoS Pathog. 2016 Oct 18;12(10):e1005937. doi: 10.1371/journal.ppat.1005937., eCollection 2016 Oct. PMID:27755595[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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