A follicle-stimulating hormone receptor ecto-domain epitope that is a target for receptor immunoneutralization yet does not affect ligand contact and activation

作者：Liu XX; Butterstein GM; Lindau Shepard B; Brumberg HA; Dias JA^*

来源：Endocrine, 2000, 13(3): 361-367.

DOI：10.1385/ENDO:13:3:361

• receptor
• ligand
• interaction
• mutagenesis
• antipeptide antibody

The follicle-stimulating hormone receptor (FSHR) large extracellular domain suggests that interaction of ligand with receptor is likely to be complex. Residues 265-296 of the FSHR are part of a sequence primarily nonhomologous with other glycoprotein hormone receptors, A reasonable hypothesis is that th is sequence of the FSHR plays a role in binding FSH, Flow cytometry studies of this region revealed that antibody X179 against peptide R265-S296 binds to human FSHR expressed by CHO cells and can be competed against by preincubating the cells with hFSH, These results suggested that the region corresponding to residues 265-296 in the extracellular domain of the FSHR is involved in binding to hormone. To test this hypothesis 10 scanning alanine mutants of rFSHR at the 265-296 epitope were generated, and the binding characteristics of these mutants were studied. Their affinity constants for I-125-hFSH did not deviate greatly from that of wild-type FSHR, in which some mutants exhibited an approximately two- to threefold reduction in K-a compared to wild-type receptor, and no mutation abolished signal transduction. These results lead to rejection of the hypothesis that this region contains residues critical for conveying hormone specificity and receptor-dependent hormone action.

• 出版日期2000-12