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Correction published on 11 December 2015, see Viruses 2015, 7(12), 6537.
Article

Conformational Ensemble of the Poliovirus 3CD Precursor Observed by MD Simulations and Confirmed by SAXS: A Strategy to Expand the Viral Proteome?

1
Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USA
2
Department of Biochemistry and Molecular Biology, St Louis University School of Medicine, 1100 South Grand Ave, St Louis, MO 63104, USA
3
Huck Institutes of life sciences, The Pennsylvania State University, University Park, PA 16802, USA
*
Authors to whom correspondence should be addressed.
Academic Editor: David Boehr
Viruses 2015, 7(11), 5962-5986; https://doi.org/10.3390/v7112919
Received: 1 June 2015 / Revised: 30 October 2015 / Accepted: 11 November 2015 / Published: 23 November 2015
The genomes of RNA viruses are relatively small. To overcome the small-size limitation, RNA viruses assign distinct functions to the processed viral proteins and their precursors. This is exemplified by poliovirus 3CD protein. 3C protein is a protease and RNA-binding protein. 3D protein is an RNA-dependent RNA polymerase (RdRp). 3CD exhibits unique protease and RNA-binding activities relative to 3C and is devoid of RdRp activity. The origin of these differences is unclear, since crystal structure of 3CD revealed “beads-on-a-string” structure with no significant structural differences compared to the fully processed proteins. We performed molecular dynamics (MD) simulations on 3CD to investigate its conformational dynamics. A compact conformation of 3CD was observed that was substantially different from that shown crystallographically. This new conformation explained the unique properties of 3CD relative to the individual proteins. Interestingly, simulations of mutant 3CD showed altered interface. Additionally, accelerated MD simulations uncovered a conformational ensemble of 3CD. When we elucidated the 3CD conformations in solution using small-angle X-ray scattering (SAXS) experiments a range of conformations from extended to compact was revealed, validating the MD simulations. The existence of conformational ensemble of 3CD could be viewed as a way to expand the poliovirus proteome, an observation that may extend to other viruses. View Full-Text
Keywords: RNA virus; poliovirus; 3CD; polyprotein; MD simulations; conformational dynamics; SAXS RNA virus; poliovirus; 3CD; polyprotein; MD simulations; conformational dynamics; SAXS
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MDPI and ACS Style

Moustafa, I.M.; Gohara, D.W.; Uchida, A.; Yennawar, N.; Cameron, C.E. Conformational Ensemble of the Poliovirus 3CD Precursor Observed by MD Simulations and Confirmed by SAXS: A Strategy to Expand the Viral Proteome? Viruses 2015, 7, 5962-5986. https://doi.org/10.3390/v7112919

AMA Style

Moustafa IM, Gohara DW, Uchida A, Yennawar N, Cameron CE. Conformational Ensemble of the Poliovirus 3CD Precursor Observed by MD Simulations and Confirmed by SAXS: A Strategy to Expand the Viral Proteome? Viruses. 2015; 7(11):5962-5986. https://doi.org/10.3390/v7112919

Chicago/Turabian Style

Moustafa, Ibrahim M.; Gohara, David W.; Uchida, Akira; Yennawar, Neela; Cameron, Craig E. 2015. "Conformational Ensemble of the Poliovirus 3CD Precursor Observed by MD Simulations and Confirmed by SAXS: A Strategy to Expand the Viral Proteome?" Viruses 7, no. 11: 5962-5986. https://doi.org/10.3390/v7112919

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