Next Article in Journal
Genetic and Phylogenetic Characterization of Tataguine and Witwatersrand Viruses and Other Orthobunyaviruses of the Anopheles A, Capim, Guamá, Koongol, Mapputta, Tete, and Turlock Serogroups
Previous Article in Journal
Fluorescent Protein Approaches in Alpha Herpesvirus Research
Previous Article in Special Issue
Nucleobase but not Sugar Fidelity is Maintained in the Sabin I RNA-Dependent RNA Polymerase
Article Menu

Export Article

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

Open AccessArticle
Viruses 2015, 7(11), 5962-5986; doi:10.3390/v7112919

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
Received: 1 June 2015 / Revised: 30 October 2015 / Accepted: 11 November 2015 / Published: 23 November 2015
View Full-Text   |   Download PDF [6258 KB, uploaded 22 December 2015]   |  

Abstract

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
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Supplementary materials

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

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.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Viruses EISSN 1999-4915 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top