Radiosequence analysis of the human progestin receptor charged with [3H]promegestone. A comparison with the glucocorticoid receptor.
Partially purified preparations of the human progestin receptor and the human and rat glucocorticoid receptor proteins were covalently charged with the synthetic progestin, [3H]promegestone, by photoaffinity labeling. After labeling, the denaturated protein was cleaved and the mixture of peptides subjected to radiosequence analysis as previously described for the rat glucocorticoid receptor protein (Carlstedt-Duke, J., Strömstedt, P.-E., Persson, B., Cederlund, E., Gustafsson, J.-A., and Jörnvall, H. (1988) J. Biol. Chem. 263, 6842-6846). The radioactivity labels identified, corresponded to Met-759 and Met-909 after photoaffinity labeling of the human progestin receptor, and Met-622 and Cys-754 after labeling of the rat glucocorticoid receptor. The residues labeled in the glucocorticoid receptor are the same as those previously reported to bind triamcinolone actonide. The corresponding residues were also labeled in the human glucocorticoid receptor. Met-759 of the progestin receptor and Met-622 of the rat glucocorticoid receptor are positioned within a segment with an overall high degree of sequence similarity and are equivalent. However, Met-909 (progestin receptor) and Cys-754 (glucocorticoid receptor) do not occur within equivalent segments of the two proteins. Thus, although the two classes of steroid hormone share a common structure within the A-ring, there are subtle differences in their interaction with the two separate receptor proteins.
Strömstedt
P E
PE
Department of Medical Nutrition, Karolinska Institutet, Huddinge University Hospital, Sweden.
Berkenstam
A
A
Jörnvall
H
H
Gustafsson
J A
JA
Carlstedt-Duke
J
J
D000345:Affinity Labels / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001943:Breast Neoplasms; D002460:Cell Line; D003545:Cysteine; D003600:Cytosol / Q000378:metabolism; D003907:Dexamethasone / Q000031:analogs & derivatives / Q000378:metabolism; D005260:Female; D006801:Humans; D008099:Liver / Q000378:metabolism; D008715:Methionine; D008969:Molecular Sequence Data; D009649:Norpregnadienes / Q000378:metabolism*; D011397:Promegestone / Q000378:metabolism*; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D011980:Receptors, Progesterone / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid; D014222:Triamcinolone Acetonide / Q000378:metabolism; D014316:Tritium
D000345:Affinity Labels; D009649:Norpregnadienes; D011965:Receptors, Glucocorticoid; D011980:Receptors, Progesterone; D014316:Tritium; D003907:Dexamethasone; D011397:Promegestone; D008715:Methionine; D014222:Triamcinolone Acetonide; D003545:Cysteine; C031710:dexamethasone 21-methanesulfonate