4PKY

ARNT/HIF transcription factor/coactivator complex

Summary for 4PKY

• Entry DOI: 10.2210/pdb4pky/pdb
• Related: 4LPZ
• Descriptor: Aryl hydrocarbon receptor nuclear translocator, Transforming acidic coiled-coil-containing protein 3, Endothelial PAS domain-containing protein 1, ... (4 entities in total)
• Functional Keywords: pas domain, arnt-hif transcription factor-coactivator complex, transcription-cell cycle complex, transcription/cell cycle
• Biological source: Homo sapiens (Human); More
• Cellular location: Nucleus: P27540 Q99814; Cytoplasm : Q9JJ11
• Total number of polymer chains: 7
• Total formula weight: 65475.53

Authors

Tomchick, D.R.,Partch, C.L.,Gardner, K.H. (deposition date: 2014-05-15, release date: 2015-02-11, Last modification date: 2024-10-16)

Primary citation

Guo, Y.,Scheuermann, T.H.,Partch, C.L.,Tomchick, D.R.,Gardner, K.H.
Coiled-coil Coactivators Play a Structural Role Mediating Interactions in Hypoxia-inducible Factor Heterodimerization.
J.Biol.Chem., 290:7707-7721, 2015

PubMed Abstract: The hypoxia-inducible factor complex (HIF-α·aryl hydrocarbon receptor nuclear translocator (ARNT)) requires association with several transcription coactivators for a successful cellular response to hypoxic stress. In addition to the conventional global transcription coactivator CREB-binding protein/p300 (CBP/p300) that binds to the HIF-α transactivation domain, a new group of transcription coactivators called the coiled-coil coactivators (CCCs) interact directly with the second PER-ARNT-SIM (PAS) domain of ARNT (ARNT PAS-B). These less studied transcription coactivators play essential roles in the HIF-dependent hypoxia response, and CCC misregulation is associated with several forms of cancer. To better understand CCC protein recruitment by the heterodimeric HIF transcription factor, we used x-ray crystallography, NMR spectroscopy, and biochemical methods to investigate the structure of the ARNT PAS-B domain in complex with the C-terminal fragment of a coiled-coil coactivator protein, transforming acidic coiled-coil coactivator 3 (TACC3). We found that the HIF-2α PAS-B domain also directly interacts with TACC3, motivating an NMR data-derived model suggesting a means by which TACC3 could form a ternary complex with HIF-2α PAS-B and ARNT PAS-B via β-sheet/coiled-coil interactions. These findings suggest that TACC3 could be recruited as a bridge to cooperatively mediate between the HIF-2α PAS-B·ARNT PAS-B complex, thereby participating more directly in HIF-dependent gene transcription than previously anticipated.

PubMed: 25627682
DOI: 10.1074/jbc.M114.632786

Experimental method

X-RAY DIFFRACTION (3.2 Å)