2N0Y

NMR structure of the complex between the C-terminal domain of the Rift Valley fever virus protein NSs and the PH domain of the Tfb1 subunit of TFIIH

Summary for 2N0Y

• Entry DOI: 10.2210/pdb2n0y/pdb
• Related: 1y5o 2lox 2m14
• NMR Information: BMRB: 25540
• Descriptor: RNA polymerase II transcription factor B subunit 1, Non-structural protein NS-S (2 entities in total)
• Functional Keywords: transcription, virulence, viral protein-transcription complex, drug target, virus-host interface, transcription-viral protein complex, transcription/viral protein
• Biological source: Saccharomyces cerevisiae (Baker's yeast); More
• Cellular location: Nucleus: P32776
• Total number of polymer chains: 2
• Total formula weight: 15470.19

Authors

Cyr, N.,de la Fuente, C.,Lecoq, L.,Guendel, I.,Chabot, P.R.,Kehn-Hall, K.,Omichinski, J.G. (deposition date: 2015-03-18, release date: 2015-04-22, Last modification date: 2024-05-15)

Primary citation

Cyr, N.,de la Fuente, C.,Lecoq, L.,Guendel, I.,Chabot, P.R.,Kehn-Hall, K.,Omichinski, J.G.
A Omega XaV motif in the Rift Valley fever virus NSs protein is essential for degrading p62, forming nuclear filaments and virulence.
Proc.Natl.Acad.Sci.USA, 112:6021-6026, 2015

PubMed Abstract: Rift Valley fever virus (RVFV) is a single-stranded RNA virus capable of inducing fatal hemorrhagic fever in humans. A key component of RVFV virulence is its ability to form nuclear filaments through interactions between the viral nonstructural protein NSs and the host general transcription factor TFIIH. Here, we identify an interaction between a ΩXaV motif in NSs and the p62 subunit of TFIIH. This motif in NSs is similar to ΩXaV motifs found in nucleotide excision repair (NER) factors and transcription factors known to interact with p62. Structural and biophysical studies demonstrate that NSs binds to p62 in a similar manner as these other factors. Functional studies in RVFV-infected cells show that the ΩXaV motif is required for both nuclear filament formation and degradation of p62. Consistent with the fact that the RVFV can be distinguished from other Bunyaviridae-family viruses due to its ability to form nuclear filaments in infected cells, the motif is absent in the NSs proteins of other Bunyaviridae-family viruses. Taken together, our studies demonstrate that p62 binding to NSs through the ΩXaV motif is essential for degrading p62, forming nuclear filaments and enhancing RVFV virulence. In addition, these results show how the RVFV incorporates a simple motif into the NSs protein that enables it to functionally mimic host cell proteins that bind the p62 subunit of TFIIH.

PubMed: 25918396
DOI: 10.1073/pnas.1503688112

Experimental method

SOLUTION NMR