4m4x | pdb_00004m4x
Structure and Dimerization Properties of the Aryl Hydrocarbon Receptor (AHR) PAS-A Domain
Structural highlights
FunctionAHR_MOUSE Ligand-activated transcriptional activator. Binds to the XRE promoter region of genes it activates. Activates the expression of multiple phase I and II xenobiotic chemical metabolizing enzyme genes (such as the CYP1A1 gene). Mediates biochemical and toxic effects of halogenated aromatic hydrocarbons. Involved in cell-cycle regulation. Likely to play an important role in the development and maturation of many tissues.[1] [2] [3] [4] [5] [6] [7] Publication Abstract from PubMedThe aryl hydrocarbon receptor (AHR) is a ligand-dependent transcription factor that binds to xenobiotics and responds by regulating the expression of gene programs required for detoxification and metabolism. AHR and its heterodimerization partner aryl hydrocarbon receptor nuclear translocator (ARNT) belong to the bHLH (basic helix-loop-helix)-PAS (PER-ARNT-SIM) family of transcription factors. Here we report the 2.55 A resolution crystal structure of the mouse AHR PAS-A domain, which represents the first AHR derived protein structure. The AHR PAS-A domain forms a helix-swapped homodimer in the crystal and also in solution. Through a detailed mutational analysis of all interface residues, we identified several hydrophobic residues that are important for the AHR dimerization and function. Our crystallographic visualization of the AHR PAS-A dimerization leads us to propose a mode of heterodimerization with ARNT that is supported by both biochemical and cell-based data. Our studies also highlight the residues of other mammalian bHLH-PAS proteins that are likely involved in their homo- or heterodimerization. Structure and Dimerization Properties of the Aryl Hydrocarbon Receptor (AHR) PAS-A Domain.,Wu D, Potluri N, Kim Y, Rastinejad F Mol Cell Biol. 2013 Sep 3. PMID:24001774[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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