4LPZ

ARNT transcription factor/coactivator complex

Summary for 4LPZ

• Entry DOI: 10.2210/pdb4lpz/pdb
• Related: 1X0O 4EQ1
• Descriptor: Aryl hydrocarbon receptor nuclear translocator, Transforming acidic coiled-coil-containing protein 3 (2 entities in total)
• Functional Keywords: pas domain coiled coil, transcription
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus: P27540
• Total number of polymer chains: 4
• Total formula weight: 38083.25

Authors

Guo, Y.,Scheuermann, T.H.,Gardner, K.H. (deposition date: 2013-07-16, release date: 2014-07-16, Last modification date: 2024-11-20)

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 (3.15 Å)