The lutropin beta-subunit N-terminus facilitates subunit combination by offsetting the inhibitory effects of residues needed for LH activity.
Human chorionic gonadotropin (hCG) contains a beta-subunit N-terminal amino acid extension that contacts the alpha-subunit and is needed for efficient alpha and hCG beta-subunit combination. Here we report that an hCG beta-subunit analog, lacking residues 2-8, combined with the alpha-subunit more efficiently when positively charged residues between beta-subunit cysteines 10 and 11 were replaced with negatively charged residues found in the corresponding portion of follitropin. Residues 2-8 had no influence on binding of hCG to lutropin receptors. Positive charges between cysteines 10 and 11 are essential for high affinity binding of lutropins to their receptors. Therefore, the N-terminal extension found in all lutropin beta-subunits appears to have evolved to offset the inhibition of subunit combination by beta-subunit residues that are essential for lutropin activity. This beta-subunit extension is not found in follitropins or thyrotropins, hormones that have negatively charged residues between cysteines 10 and 11.
Slaughter
S
S
Department of OBGYN, Robert Wood Johnson (Rutgers) Medical School, Piscataway, NJ 08854, USA.
Wang
Y
Y
Myers
R V
RV
Moyle
W R
WR
D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D006063:Chorionic Gonadotropin / Q000378:metabolism; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004563:Electrochemistry; D015292:Glycoprotein Hormones, alpha Subunit / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007986:Luteinizing Hormone / Q000494:pharmacology* / Q000502:physiology*; D008969:Molecular Sequence Data; D016296:Mutagenesis; D010446:Peptide Fragments / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D011974:Receptors, LH / Q000378:metabolism; D014162:Transfection
D006063:Chorionic Gonadotropin; D018997:Chorionic Gonadotropin, beta Subunit, Human; D015292:Glycoprotein Hormones, alpha Subunit; D010446:Peptide Fragments; D011974:Receptors, LH; D007986:Luteinizing Hormone; D000242:Cyclic AMP