L. Cosowsky et al., INFLUENCE OF SUBUNIT INTERACTIONS ON LUTROPIN SPECIFICITY - IMPLICATIONS FOR STUDIES OF GLYCOPROTEIN HORMONE FUNCTION, The Journal of biological chemistry, 272(6), 1997, pp. 3309-3314
Bovine lutropin (bLH) and human chorionic gonadotropin (hCG) are heter
odimeric glycoprotein hormones required for reproduction. Both bind ra
t LH receptors (rLHRs), but hCG binds human LH receptors (hLHRs) 1000-
10,000 fold better than bLH. We tested the premise that this differenc
e in affinity could be used to identify lutropin receptor contacts. He
terodimers containing hCG/bLH alpha- or beta-subunit chimeras that bou
nd hLHR like hCG (or bLH) were expected to have hCG (or bLH) residues
at the receptor contact sites. Analogs containing one subunit derived
from hCG bound hLHR, much more like hCG than bLH, indicating that each
bLH subunit contains all the residues sufficient for high affinity hL
HR binding. Indeed, the presence of bovine alpha-subunit residues incr
eased the activities of some hCG analogs. The low hLHR activity of bLH
was due primarily to an interaction between its alpha-subunit and bet
a-subunit residue Leu(95). Leu(95) does not appear to contact the hLHR
since it did not influence the hLHR activity of heterodimers containi
ng human alpha-subunit. These observations show that interactions with
in and between the subunits can significantly influence the activities
of lutropins, thereby confounding efforts to identify ligand residues
that contact these receptors.