4zpk

Crystal Structure of the Heterodimeric HIF-2a:ARNT Complex with HRE DNA

spinqualitylabelsall models 4zpk, resolution 3.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4zpk is a 4 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.6Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ARNT_MOUSE 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 (By similarity). Publication Abstract from PubMed The hypoxia-inducible factors (HIFs) coordinate cellular adaptations to low oxygen stress by regulating transcriptional programs in erythropoiesis, angiogenesis and metabolism. These programs promote the growth and progression of many tumours, making HIFs attractive anticancer targets. Transcriptionally active HIFs consist of HIF-alpha and ARNT (also called HIF-1beta) subunits. Here we describe crystal structures for each of mouse HIF-2alpha-ARNT and HIF-1alpha-ARNT heterodimers in states that include bound small molecules and their hypoxia response element. A highly integrated quaternary architecture is shared by HIF-2alpha-ARNT and HIF-1alpha-ARNT, wherein ARNT spirals around the outside of each HIF-alpha subunit. Five distinct pockets are observed that permit small-molecule binding, including PAS domain encapsulated sites and an interfacial cavity formed through subunit heterodimerization. The DNA-reading head rotates, extends and cooperates with a distal PAS domain to bind hypoxia response elements. HIF-alpha mutations linked to human cancers map to sensitive sites that establish DNA binding and the stability of PAS domains and pockets. Structural integration in hypoxia-inducible factors.,Wu D, Potluri N, Lu J, Kim Y, Rastinejad F Nature. 2015 Aug 5. doi: 10.1038/nature14883. PMID:26245371 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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