AFF4 binding to Tat-P-TEFb indirectly stimulates TAR recognition of super elongation complexes at the HIV promoter
Superelongation complexes (SECs) are essential for transcription elongation of many human genes, including the integrated HIV-1 genome. At the HIV-1 promoter, the viral Tat protein binds simultaneously to the nascent TAR RNA and the CycT1 subunit of the P-TEFb kinase in a SEC. To understand the pref...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2014-04-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/02375 |
| _version_ | 1811201054769938432 |
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| author | Ursula Schulze-Gahmen Huasong Lu Qiang Zhou Tom Alber |
| author_facet | Ursula Schulze-Gahmen Huasong Lu Qiang Zhou Tom Alber |
| author_sort | Ursula Schulze-Gahmen |
| collection | DOAJ |
| description | Superelongation complexes (SECs) are essential for transcription elongation of many human genes, including the integrated HIV-1 genome. At the HIV-1 promoter, the viral Tat protein binds simultaneously to the nascent TAR RNA and the CycT1 subunit of the P-TEFb kinase in a SEC. To understand the preferential recruitment of SECs by Tat and TAR, we determined the crystal structure of a quaternary complex containing Tat, P-TEFb, and the SEC scaffold, AFF4. Tat and AFF4 fold on the surface of CycT1 and interact directly. Interface mutations in the AFF4 homolog AFF1 reduced Tat–AFF1 affinity in vivo and Tat-dependent transcription from the HIV promoter. AFF4 binding in the presence of Tat partially orders the CycT1 Tat–TAR recognition motif and increases the affinity of Tat-P-TEFb for TAR 30-fold. These studies indicate that AFF4 acts as a two-step filter to increase the selectivity of Tat and TAR for SECs over P-TEFb alone. |
| first_indexed | 2024-04-12T02:14:26Z |
| format | Article |
| id | doaj.art-41299cae61c448059c6429a27fbd39af |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T02:14:26Z |
| publishDate | 2014-04-01 |
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| spelling | doaj.art-41299cae61c448059c6429a27fbd39af2022-12-22T03:52:17ZengeLife Sciences Publications LtdeLife2050-084X2014-04-01310.7554/eLife.02375AFF4 binding to Tat-P-TEFb indirectly stimulates TAR recognition of super elongation complexes at the HIV promoterUrsula Schulze-Gahmen0Huasong Lu1Qiang Zhou2Tom Alber3Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United StatesDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United StatesDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United StatesDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States; California Institute for Quantitative Biosciences, QB3, University of California, Berkeley, Berkeley, United StatesSuperelongation complexes (SECs) are essential for transcription elongation of many human genes, including the integrated HIV-1 genome. At the HIV-1 promoter, the viral Tat protein binds simultaneously to the nascent TAR RNA and the CycT1 subunit of the P-TEFb kinase in a SEC. To understand the preferential recruitment of SECs by Tat and TAR, we determined the crystal structure of a quaternary complex containing Tat, P-TEFb, and the SEC scaffold, AFF4. Tat and AFF4 fold on the surface of CycT1 and interact directly. Interface mutations in the AFF4 homolog AFF1 reduced Tat–AFF1 affinity in vivo and Tat-dependent transcription from the HIV promoter. AFF4 binding in the presence of Tat partially orders the CycT1 Tat–TAR recognition motif and increases the affinity of Tat-P-TEFb for TAR 30-fold. These studies indicate that AFF4 acts as a two-step filter to increase the selectivity of Tat and TAR for SECs over P-TEFb alone.https://elifesciences.org/articles/02375crystal structuretranscriptional elongationTat-AFF4-CycT1 interfaceTat-TAR recognition motif |
| spellingShingle | Ursula Schulze-Gahmen Huasong Lu Qiang Zhou Tom Alber AFF4 binding to Tat-P-TEFb indirectly stimulates TAR recognition of super elongation complexes at the HIV promoter eLife crystal structure transcriptional elongation Tat-AFF4-CycT1 interface Tat-TAR recognition motif |
| title | AFF4 binding to Tat-P-TEFb indirectly stimulates TAR recognition of super elongation complexes at the HIV promoter |
| title_full | AFF4 binding to Tat-P-TEFb indirectly stimulates TAR recognition of super elongation complexes at the HIV promoter |
| title_fullStr | AFF4 binding to Tat-P-TEFb indirectly stimulates TAR recognition of super elongation complexes at the HIV promoter |
| title_full_unstemmed | AFF4 binding to Tat-P-TEFb indirectly stimulates TAR recognition of super elongation complexes at the HIV promoter |
| title_short | AFF4 binding to Tat-P-TEFb indirectly stimulates TAR recognition of super elongation complexes at the HIV promoter |
| title_sort | aff4 binding to tat p tefb indirectly stimulates tar recognition of super elongation complexes at the hiv promoter |
| topic | crystal structure transcriptional elongation Tat-AFF4-CycT1 interface Tat-TAR recognition motif |
| url | https://elifesciences.org/articles/02375 |
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