4OGR

crystal structure of P-TEFb complex with AFF4 and Tat

Summary for 4OGR

• Entry DOI: 10.2210/pdb4ogr/pdb
• Descriptor: Cyclin-dependent kinase 9, Cyclin-T1, AF4/FMR2 family member 4, ... (7 entities in total)
• Functional Keywords: p-tefb, cyclin-dependent kinase 9, cyclin fold, intrinsically unstructured aff4, transcriptional regulation at hiv promoter, binds tar, n-terminal acetylation of tat, transferase-viral protein complex, transferase/viral protein
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus: P50750 O60563 Q9UHB7; Host nucleus, host nucleolus : P69698
• Total number of polymer chains: 12
• Total formula weight: 254451.64

Authors

Schulze-Gahmen, U.,Alber, T. (deposition date: 2014-01-16, release date: 2014-05-07, Last modification date: 2024-11-20)

Primary citation

Schulze-Gahmen, U.,Lu, H.,Zhou, Q.,Alber, T.
AFF4 binding to Tat-P-TEFb indirectly stimulates TAR recognition of super elongation complexes at the HIV promoter.
Elife, 3:e02375-e02375, 2014

PubMed Abstract: 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.DOI: http://dx.doi.org/10.7554/eLife.02375.001.

PubMed: 24843025
DOI: 10.7554/eLife.02375

Experimental method

X-RAY DIFFRACTION (3 Å)