Reduced steroid activation of elephant shark GR and MR after inserting four amino acids from the DNA-binding domain of lamprey corticoid receptor-1

• Published in: PloS one Vol. 18; no. 8; p. e0290159
• Main Authors: Katsu, Yoshinao, Zhang, Jiawen, Baker, Michael E
• Format: Journal Article
• Language: English
• Published: San Francisco Public Library of Science 23.08.2023; Public Library of Science (PLoS)
• Subjects: Aldosterone; Amino acids; Analysis; Binding; Biology and Life Sciences; Corticoids; Corticosteroids; Corticosterone; Deoxyribonucleic acid; Diseases; DNA; DNA binding proteins; Dosage and administration; Genetic aspects; Genetic transcription; Genomes; Glucocorticoid receptors; Glucocorticoids; Glutamine; Glycine; Growth; Hormones; Mineralocorticoid receptors; Physical Sciences; Physiology; Plasmids; Protein expression; Proteins; Receptors; Research and Analysis Methods; Residues; Sea lamprey; Sharks; Steroid hormones; Steroids; Transcription activation; Transcription factors; Vertebrates; United States
• DOI: 10.1371/journal.pone.0290159
• ISSN: 1932-6203

Atlantic sea lamprey contains two corticoid receptors (CRs), CR1 and CR2, that have identical amino acid sequences, except for a four amino acid insert (Thr-Arg-Gln-Gly) in the CR1 DNA-binding domain (DBD). Steroids are stronger transcriptional activators of CR2 than of CR1 suggesting that the insert reduces the transcriptional response of lamprey CR1 to steroids. The DBD in elephant shark mineralocorticoid receptor (MR) and glucocorticoid receptor (GR), which are descended from a CR, lack these four amino acids, suggesting that a CR2 is their common ancestor. To determine if, similar to lamprey CR1, the presence of this insert in elephant shark MR and GR decreases transcriptional activation by corticosteroids, we inserted these four CR1-specific residues into the DBD of elephant shark MR and GR. Compared to steroid activation of wild-type elephant shark MR and GR, cortisol, corticosterone, aldosterone, 11-deoxycorticosterone and 11-deoxycortisol had lower transcriptional activation of these mutant MR and GR receptors, indicating that the absence of this four-residue segment in the DBD in wild-type elephant shark MR and GR increases transcriptional activation by corticosteroids.