eLife, 2016-10, Vol.5
2016
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- Autor(en) / Beteiligte
- Titel
- Insights into HIV-1 proviral transcription from integrative structure and dynamics of the Tat:AFF4:P-TEFb:TAR complex
- Ist Teil von
- eLife, 2016-10, Vol.5
- Ort / Verlag
- England: eLife Sciences Publications Ltd
- Erscheinungsjahr
- 2016
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- HIV-1 Tat hijacks the human superelongation complex (SEC) to promote proviral transcription. Here we report the 5.9 Å structure of HIV-1 TAR in complex with HIV-1 Tat and human AFF4, CDK9, and CycT1. The TAR central loop contacts the CycT1 Tat-TAR recognition motif (TRM) and the second Tat Zn -binding loop. Hydrogen-deuterium exchange (HDX) shows that AFF4 helix 2 is stabilized in the TAR complex despite not touching the RNA, explaining how it enhances TAR binding to the SEC 50-fold. RNA SHAPE and SAXS data were used to help model the extended (Tat Arginine-Rich Motif) ARM, which enters the TAR major groove between the bulge and the central loop. The structure and functional assays collectively support an integrative structure and a bipartite binding model, wherein the TAR central loop engages the CycT1 TRM and compact core of Tat, while the TAR major groove interacts with the extended Tat ARM.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2050-084XeISSN: 2050-084XDOI: 10.7554/eLife.15910Titel-ID: cdi_doaj_primary_oai_doaj_org_article_31e1d27483494283b8b90982f215bc2a
- Format
- –
- Schlagworte
- Arginine, BASIC BIOLOGICAL SCIENCES, Biochemistry, Biophysics and Structural Biology, Crystal structure, Cyclin T - chemistry, Cyclin T - metabolism, Cyclin-Dependent Kinase 9 - chemistry, Cyclin-Dependent Kinase 9 - metabolism, Deuterium Exchange Measurement, DNA, Viral - chemistry, DNA, Viral - metabolism, HDX, HIV, HIV Long Terminal Repeat, HIV-1 - genetics, Human immunodeficiency virus, Humans, Hydrogen-deuterium exchange, integrative modeling, Life Sciences & Biomedicine - Other Topics, Magnetic Resonance Spectroscopy, Medical research, Models, Molecular, Proteins, Proviruses - genetics, Repressor Proteins - chemistry, Repressor Proteins - metabolism, Ribonucleic acid, RNA, SAXS, Scattering, Small Angle, SHAPE, Solvents, tat Gene Products, Human Immunodeficiency Virus - chemistry, tat Gene Products, Human Immunodeficiency Virus - metabolism, Tat protein, Transcription, Transcription, Genetic, Transcriptional Elongation Factors - chemistry, Transcriptional Elongation Factors - metabolism, X-ray crystallography, Zinc