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• W2000965610 endingPage "400" @default.
• W2000965610 startingPage "392" @default.
• W2000965610 abstract "The cytosolic transcription factor known as the aryl hydrocarbon receptor (AhR) undergoes transformation to a DNA-binding form by a series of processes initiated by binding of ligand. Subsequent steps include dissociation of several proteins that are complexed with the inactive receptor, nuclear translocation, and dimerization with Arnt. We have used limited proteolysis of the in vitro-translated mouse AhR to determine whether this technique can detect conformational change(s) associated with AhR transformation and whether the effect of agonist and antagonist ligands can be distinguished by this assay. Limited digestion of [³⁵S]AhR/AhR nuclear translocator (Arnt) by trypsin produced a peptide of approximately 40 kDa that was more resistant to proteolysis in the presence of 2,3,7,8-tetrachlorodibenzo-<i>p</i>-dioxin (TCDD) than vehicle and was also Arnt-dependent. This trypsin-resistant peptide was also elicited in the presence of other agonist ligands, but not with antagonist ligands that do not form the DNA-binding AhR/Arnt complex. Immunoblot of trypsin-treated AhR/Arnt ± TCDD indicated that the trypsin-resistant peptide did not include the N-terminal portion of the AhR against which the antibody was made. Truncated AhRs were also subjected to limited trypsinization. From AhR(1–399), a TCDD-dependent peptide of approximately 35 kDa was observed; from the constitutively active AhR(1–348), a band of approximately 30 kDa was produced from vehicle- and TCDD-treated protein. From these observations, we hypothesize that the trypsin-resistant peptide from full-length AhR spans approximately from amino acid 80 to 440. We conclude that agonist ligands initiate structural alteration in AhR that is Arnt-dependent and at least partially involves the ligand-binding/Per-Arnt-Sim domain." @default.
• W2000965610 created "2016-06-24" @default.
• W2000965610 creator A5025119335 @default.
• W2000965610 creator A5060934008 @default.
• W2000965610 date "2003-02-01" @default.
• W2000965610 modified "2023-10-15" @default.
• W2000965610 title "Agonist but Not Antagonist Ligands Induce Conformational Change in the Mouse Aryl Hydrocarbon Receptor as Detected by Partial Proteolysis" @default.
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• W2000965610 doi "https://doi.org/10.1124/mol.63.2.392" @default.
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