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Article
Structural Model of the Rev Regulatory Protein from Equine Infectious Anemia Virus
PloS ONE
  • Yungok Ihm, Iowa State University
  • Wendy O. Sparks, Iowa State University
  • Jae-Hyung Lee, Iowa State University
  • Haibo Cao, Iowa State University
  • Susan Carpenter, Iowa State University
  • Cai-Zhuang Wang, Iowa State University
  • Kai-Ming Ho, Iowa State University
  • Drena Dobbs, Iowa State University
Document Type
Article
Publication Version
Published Version
Publication Date
1-1-2009
DOI
10.1371/journal.pone.0004178
Abstract
Rev is an essential regulatory protein in the equine infectious anemia virus (EIAV) and other lentiviruses, including HIV-1. It binds incompletely spliced viral mRNAs and shuttles them from the nucleus to the cytoplasm, a critical prerequisite for the production of viral structural proteins and genomic RNA. Despite its important role in production of infectious virus, the development of antiviral therapies directed against Rev has been hampered by the lack of an experimentally-determined structure of the full length protein. We have used a combined computational and biochemical approach to generate and evaluate a structural model of the Rev protein. The modeled EIAV Rev (ERev) structure includes a total of 6 helices, four of which form an anti-parallel four-helix bundle. The first helix contains the leucine-rich nuclear export signal (NES). An arginine-rich RNA binding motif, RRDRW, is located in a solvent-exposed loop region. An ERLE motif required for Rev activity is predicted to be buried in the core of modeled structure where it plays an essential role in stabilization of the Rev fold. This structural model is supported by existing genetic and functional data as well as by targeted mutagenesis of residues predicted to be essential for overall structural integrity. Our predicted structure should increase understanding of structure-function relationships in Rev and may provide a basis for the design of new therapies for lentiviral diseases.
Comments

This article is from PloS ONE 4 (2009): e4178, doi: 10.1371/journal.pone.0004178. Posted with permission.

Rights
This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Copyright Owner
Ihm et al.
Language
en
File Format
application/pdf
Citation Information
Yungok Ihm, Wendy O. Sparks, Jae-Hyung Lee, Haibo Cao, et al.. "Structural Model of the Rev Regulatory Protein from Equine Infectious Anemia Virus" PloS ONE Vol. 4 Iss. 1 (2009) p. e4178
Available at: http://works.bepress.com/drena-dobbs/41/