Implications of the HIV-1 Rev dimer structure at 3.2 A resolution for multimeric binding to the Rev response element.

HIV-1 Rev is a small regulatory protein that mediates the nuclear export of viral mRNAs, an essential step in the HIV replication cycle. In this process Rev oligomerizes in association with a highly structured RNA motif, the Rev response element. Crystallographic studies of Rev have been hampered by...

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Main Authors: DiMattia, M, Watts, N, Stahl, S, Rader, C, Wingfield, P, Stuart, D, Steven, A, Grimes, J
Formato: Journal article
Idioma:English
Publicado em: 2010
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author DiMattia, M
Watts, N
Stahl, S
Rader, C
Wingfield, P
Stuart, D
Steven, A
Grimes, J
author_facet DiMattia, M
Watts, N
Stahl, S
Rader, C
Wingfield, P
Stuart, D
Steven, A
Grimes, J
author_sort DiMattia, M
collection OXFORD
description HIV-1 Rev is a small regulatory protein that mediates the nuclear export of viral mRNAs, an essential step in the HIV replication cycle. In this process Rev oligomerizes in association with a highly structured RNA motif, the Rev response element. Crystallographic studies of Rev have been hampered by the protein's tendency to aggregate, but Rev has now been found to form a stable soluble equimolar complex with a specifically engineered monoclonal Fab fragment. We have determined the structure of this complex at 3.2 A resolution. It reveals a molecular dimer of Rev, bound on either side by a Fab, where the ordered portion of each Rev monomer (residues 9-65) contains two coplanar alpha-helices arranged in hairpin fashion. Subunits dimerize through overlapping of the hairpin prongs. Mating of hydrophobic patches on the outer surface of the dimer is likely to promote higher order interactions, suggesting a model for Rev oligomerization onto the viral RNA.
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spelling oxford-uuid:789fbf4a-29d8-407b-b2ae-1304322d6f3d2022-03-26T20:31:56ZImplications of the HIV-1 Rev dimer structure at 3.2 A resolution for multimeric binding to the Rev response element.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:789fbf4a-29d8-407b-b2ae-1304322d6f3dEnglishSymplectic Elements at Oxford2010DiMattia, MWatts, NStahl, SRader, CWingfield, PStuart, DSteven, AGrimes, JHIV-1 Rev is a small regulatory protein that mediates the nuclear export of viral mRNAs, an essential step in the HIV replication cycle. In this process Rev oligomerizes in association with a highly structured RNA motif, the Rev response element. Crystallographic studies of Rev have been hampered by the protein's tendency to aggregate, but Rev has now been found to form a stable soluble equimolar complex with a specifically engineered monoclonal Fab fragment. We have determined the structure of this complex at 3.2 A resolution. It reveals a molecular dimer of Rev, bound on either side by a Fab, where the ordered portion of each Rev monomer (residues 9-65) contains two coplanar alpha-helices arranged in hairpin fashion. Subunits dimerize through overlapping of the hairpin prongs. Mating of hydrophobic patches on the outer surface of the dimer is likely to promote higher order interactions, suggesting a model for Rev oligomerization onto the viral RNA.
spellingShingle DiMattia, M
Watts, N
Stahl, S
Rader, C
Wingfield, P
Stuart, D
Steven, A
Grimes, J
Implications of the HIV-1 Rev dimer structure at 3.2 A resolution for multimeric binding to the Rev response element.
title Implications of the HIV-1 Rev dimer structure at 3.2 A resolution for multimeric binding to the Rev response element.
title_full Implications of the HIV-1 Rev dimer structure at 3.2 A resolution for multimeric binding to the Rev response element.
title_fullStr Implications of the HIV-1 Rev dimer structure at 3.2 A resolution for multimeric binding to the Rev response element.
title_full_unstemmed Implications of the HIV-1 Rev dimer structure at 3.2 A resolution for multimeric binding to the Rev response element.
title_short Implications of the HIV-1 Rev dimer structure at 3.2 A resolution for multimeric binding to the Rev response element.
title_sort implications of the hiv 1 rev dimer structure at 3 2 a resolution for multimeric binding to the rev response element
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