7v7l | pdb_00007v7l

Crystal Structure of the Heterodimeric HIF-3a:ARNT Complex

spinqualitylabelsall models 7v7l, resolution 2.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7v7l is a 2 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 2.3Å 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 Hypoxia-inducible factors (HIFs) are alpha/beta heterodimeric transcription factors modulating cellular responses to the low oxygen condition. Among three HIF-alpha isoforms, HIF-3alpha is the least studied to date. Here we show that oleoylethanolamide (OEA), a physiological lipid known to regulate food intake and metabolism, binds selectively to HIF-3alpha. Through crystallographic analysis of HIF-3 alpha/beta heterodimer in both apo and OEA-bound forms, hydrogen-deuterium exchange mass spectrometry (HDX-MS), molecular dynamics (MD) simulations, and biochemical and cell-based assays, we unveil the molecular mechanism of OEA entry and binding to the PAS-B pocket of HIF-3alpha, and show that it leads to enhanced heterodimer stability and functional modulation of HIF-3. The identification of HIF-3alpha as a selective lipid sensor is consistent with recent human genetic findings linking HIF-3alpha with obesity, and demonstrates that endogenous metabolites can directly interact with HIF-alpha proteins to modulate their activities, potentially as a regulatory mechanism supplementary to the well-known oxygen-dependent HIF-alpha hydroxylation. Identification of oleoylethanolamide as an endogenous ligand for HIF-3alpha.,Diao X, Ye F, Zhang M, Ren X, Tian X, Lu J, Sun X, Hou Z, Chen X, Li F, Zhuang J, Ding H, Peng C, Rastinejad F, Luo C, Wu D Nat Commun. 2022 May 9;13(1):2529. doi: 10.1038/s41467-022-30338-z. PMID:35534502 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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