4lpz

ARNT transcription factor/coactivator complex

spinqualitylabelsall models 4lpz, resolution 3.15Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4lpz is a 4 chain structure with sequence from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.15Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ARNT_HUMAN Required for activity of the Ah (dioxin) receptor. This protein is required for the ligand-binding subunit to translocate from the cytosol to the nucleus after ligand binding. The complex then initiates transcription of genes involved in the activation of PAH procarcinogens. The heterodimer with HIF1A or EPAS1/HIF2A functions as a transcriptional regulator of the adaptive response to hypoxia. Publication Abstract from PubMed The hypoxia inducible factor complex (HIF-alpha/ARNT) requires association with several transcription coactivators for a successful cellular response to hypoxic stress. In addition to the conventional global transcription coactivator CBP/p300 that binds to the HIF-alpha transactivation domain (TAD), 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 CCCs 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-2alpha 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-2alpha PAS-B and ARNT PAS-B via beta-sheet/coiled-coil interactions. These findings suggest that TACC3 could be recruited as a bridge to cooperatively mediate between the HIF-2alpha PAS-B/ARNT PAS-B complex, therefore participating more directly in HIF-dependent gene transcription than previously anticipated. Coiled-coil Coactivators Play a Structural Role Mediating Interactions in Hypoxia Inducible Factor Heterodimerization.,Guo Y, Scheuermann TH, Partch CL, Tomchick DR, Gardner KH J Biol Chem. 2015 Jan 27. pii: jbc.M114.632786. PMID:25627682 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also 3D structures of hypoxia-inducible factor

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