4IMY

The AFF4 scaffold binds human P-TEFb adjacent to HIV Tat

Summary for 4IMY

• Entry DOI: 10.2210/pdb4imy/pdb
• Descriptor: Cyclin-dependent kinase 9, Cyclin-T1, AF4/FMR2 family member 4, ... (5 entities in total)
• Functional Keywords: transcriptional cdk9-cyct1 complex, phosphorylated, intrinsically disordered aff4, regulation of transcription elongation, ser/thr kinase, phosphorylation of polii-ctd, dsif, and nelf, hiv-1 tat, host-virus interaction, phosphoprotein, nucleus, transferase
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus: P50750 O60563 Q9UHB7
• Total number of polymer chains: 9
• Total formula weight: 233946.80

Authors

Alber, T.,Schulze-Gahmen, U. (deposition date: 2013-01-03, release date: 2013-03-13, Last modification date: 2024-11-20)

Primary citation

Schulze-Gahmen, U.,Upton, H.,Birnberg, A.,Bao, K.,Chou, S.,Krogan, N.J.,Zhou, Q.,Alber, T.
The AFF4 scaffold binds human P-TEFb adjacent to HIV Tat.
Elife, 2:e00327-e00327, 2013

PubMed Abstract: Human positive transcription elongation factor b (P-TEFb) phosphorylates RNA polymerase II and regulatory proteins to trigger elongation of many gene transcripts. The HIV-1 Tat protein selectively recruits P-TEFb as part of a super elongation complex (SEC) organized on a flexible AFF1 or AFF4 scaffold. To understand this specificity and determine if scaffold binding alters P-TEFb conformation, we determined the structure of a tripartite complex containing the recognition regions of P-TEFb and AFF4. AFF4 meanders over the surface of the P-TEFb cyclin T1 (CycT1) subunit but makes no stable contacts with the CDK9 kinase subunit. Interface mutations reduced CycT1 binding and AFF4-dependent transcription. AFF4 is positioned to make unexpected direct contacts with HIV Tat, and Tat enhances P-TEFb affinity for AFF4. These studies define the mechanism of scaffold recognition by P-TEFb and reveal an unanticipated intersubunit pocket on the AFF4 SEC that potentially represents a target for therapeutic intervention against HIV/AIDS. DOI:http://dx.doi.org/10.7554/eLife.00327.001.

PubMed: 23471103
DOI: 10.7554/eLife.00327

Experimental method

X-RAY DIFFRACTION (2.94 Å)