Structural model of the Rev regulatory protein from equine infectious anemia virus.
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 geno...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2009-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2613556?pdf=render |
| _version_ | 1818359162368688128 |
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| author | Yungok Ihm Wendy O Sparks Jae-Hyung Lee Haibo Cao Susan Carpenter Cai-Zhuang Wang Kai-Ming Ho Drena Dobbs |
| author_facet | Yungok Ihm Wendy O Sparks Jae-Hyung Lee Haibo Cao Susan Carpenter Cai-Zhuang Wang Kai-Ming Ho Drena Dobbs |
| author_sort | Yungok Ihm |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-13T20:40:31Z |
| format | Article |
| id | doaj.art-bfbca4ab6f5448a9ada0b1f07b25ca25 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T20:40:31Z |
| publishDate | 2009-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-bfbca4ab6f5448a9ada0b1f07b25ca252022-12-21T23:32:09ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-01-0141e417810.1371/journal.pone.0004178Structural model of the Rev regulatory protein from equine infectious anemia virus.Yungok IhmWendy O SparksJae-Hyung LeeHaibo CaoSusan CarpenterCai-Zhuang WangKai-Ming HoDrena DobbsRev 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.http://europepmc.org/articles/PMC2613556?pdf=render |
| spellingShingle | Yungok Ihm Wendy O Sparks Jae-Hyung Lee Haibo Cao Susan Carpenter Cai-Zhuang Wang Kai-Ming Ho Drena Dobbs Structural model of the Rev regulatory protein from equine infectious anemia virus. PLoS ONE |
| title | Structural model of the Rev regulatory protein from equine infectious anemia virus. |
| title_full | Structural model of the Rev regulatory protein from equine infectious anemia virus. |
| title_fullStr | Structural model of the Rev regulatory protein from equine infectious anemia virus. |
| title_full_unstemmed | Structural model of the Rev regulatory protein from equine infectious anemia virus. |
| title_short | Structural model of the Rev regulatory protein from equine infectious anemia virus. |
| title_sort | structural model of the rev regulatory protein from equine infectious anemia virus |
| url | http://europepmc.org/articles/PMC2613556?pdf=render |
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