Characterization of a critical region in the hormone binding domain of sperm progesterone receptor.
Our previous studies have demonstrated that the ligand binding characteristics of the non-genomic sperm progesterone receptor (sPR) are different from those of the conventional progesterone receptor (PR). Unlike PR, sPR does not bind efficiently to progesterone antagonists i.e. mifepristone (RU38486), onapristone (ZK98.299) etc. The present study was undertaken to determine the molecular composition of a region that plays a critical role in the interaction of the hormone-binding domain (HBD) of sPR with progesterone and its antagonists. Detection, cloning and sequencing of the HBD region of sPR revealed its complete sequence homology to the corresponding region in the conventional PR. No nucleotide substitution/mutation/deletion, which could account for the differential antihormone binding, was observed in the HBD of sPR. The critical codon (nucleotide 3216-3218) in all three clones for the HBD of sPR was found to encode for glycine. This ruled out the possibility of steric hindrance because of the placement of amino acids with side chains at a critical position in the HBD, which may interfere in binding of sPR with antiprogestins. It is likely that the post-transcriptional modifications contribute to the differential binding characteristics of sPR. This warrants future investigations to focus more on the characterization of the mature sPR protein.
Sachdeva
Geetanjali
G
National Institute for Research in Reproductive Health, Indian Council of Medical Research, Parel, Mumbai 400 012, India.
Gadkar
Sushama
S
Shah
Chirag Ashwinkumar
CA
Kholkute
Sanjiva Dattatraya
SD
Puri
Chander Prakash
CP
D001483:Base Sequence; D015139:Blotting, Southern; D017931:DNA Primers; D004717:Endometrium / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D011374:Progesterone / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017434:Protein Structure, Tertiary / Q000502:physiology*; D011980:Receptors, Progesterone / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013094:Spermatozoa / Q000378:metabolism*
D017931:DNA Primers; D011980:Receptors, Progesterone; D011374:Progesterone