ZFIN ID: ZDB-PUB-020220-17
Identification of a critical amino acid in the Aryl hydrocarbon receptor
Andreasen, E.A., Tanguay, R.L., Peterson, R.E., and Heideman, W.
Date: 2002
Source: The Journal of biological chemistry   277(15): 13210-13218 (Journal)
Registered Authors: Andreasen, Eric A., Heideman, Warren, Peterson, Richard E., Tanguay, Robyn L.
Keywords: none
MeSH Terms:
  • Amino Acid Sequence
  • Amino Acid Substitution
  • Amino Acids/metabolism*
  • Animals
  • Base Sequence
  • COS Cells
  • DNA Primers
  • Models, Molecular
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Oncorhynchus mykiss
  • Protein Conformation
  • Receptors, Aryl Hydrocarbon/chemistry
  • Receptors, Aryl Hydrocarbon/genetics
  • Receptors, Aryl Hydrocarbon/metabolism*
  • Sequence Homology, Amino Acid
PubMed: 11823471 Full text @ J. Biol. Chem.
Two aryl hydrocarbon receptors (rtAHR2[alpha] and rtAHR2[beta]) have been identified in the rainbow trout (Oncorhynchus mykiss). These receptors share 98% amino acid identity, yet their functional properties differ. Both rtAHR2[alpha] and rtAHR2[beta] bind 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD), dimerize with rainbow trout ARNTb (rtARNTb), and recognize dioxin response elements in vitro. However, in a transient transfection assay the two proteins show differential ability to recognize enhancer elements, produce transactivation, and respond to TCDD. To identify the sequence differences that confer the functional differences between rtAHR2[alpha] and rtAHR2[beta] we constructed chimeric rtAHRs, in which segments of one receptor form was replaced with the corresponding part from the other isoform. This approach progressively narrowed the region being examined to a single residue, corresponding to position 111 in rtAHR2[beta]. Altering this residue in rtAHR2[beta] from the lysine to glutamate found in rtAHR2[alpha] produced an rtAHR2[beta] with the properties of rtAHR2[alpha]. All other known AHRs resemble rtAHR2[alpha], and carry glutamate at this position, located at the N-terminus of the PAS domain. We tested the effect of altering this glutamate in the human and zebrafish AHRs to lysine. This lysine substitution produced AHRs with transactivation properties that were similar to rtAHR2[beta]. These results identify a critical residue in AHR proteins that has an important impact on transactivation, enhancer site recognition, and regulation by ligand.