Localization of residues that confer antibody binding specificity using human chorionic gonadotropin/luteinizing hormone β subunit chimeras and mutants

W. R. Moyle, M. M. Matzuk, R. K. Campbell, E. Cogliani, D. M. Dean-Emig, A. Krichevsky, R. W. Barnett, I. Boime

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72 Scopus citations

Abstract

The glycoprotein hormones are a family of conserved heterodimeric proteins which share a common α subunit but differ in their hormone-specific β subunits. We used chimeras of human chorionic gonadotropin (hCG) and luteinizing hormone (hLH) β subunits to identify residues which enable monoclonal antibodies (mAb) to distinguish the two hormones. The LHβ-CGβ chimeras appeared to fold similar to hCGβ, since they combined with hCGα and, depending on their sequences, were recognized by hCG-selective mAbs. Amino acid residues Arg8-Arg10, Gly47-Ala51, and Gln89-Leu92 form a major epitope region and appear to be adjacent to each other on the surface of hCGβ. Gly47-Ala51 and Gln89-Leu92 are recognized by dimer-specific mAbs while Arg8-Arg10 is recognized by mAbs which have highest affinity for the free β subunit. These observations suggest that the conformation of this region of the β subunit changes when the α and β subunits combine. Residues which are C-terminal of Asp112 form a second epitope domain. mAbs to the third domain distinguish hCGβ and hLHβ by the presence of Asn77 in HcGβ and can be detected after hCG binds to receptors. These findings were used to develop a model of hCGβ which predicts the locations of these residues and their positions relative to the α subunit and receptor interfaces.

Original languageEnglish
Pages (from-to)8511-8518
Number of pages8
JournalJournal of Biological Chemistry
Volume265
Issue number15
StatePublished - Jun 12 1990
Externally publishedYes

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    Moyle, W. R., Matzuk, M. M., Campbell, R. K., Cogliani, E., Dean-Emig, D. M., Krichevsky, A., Barnett, R. W., & Boime, I. (1990). Localization of residues that confer antibody binding specificity using human chorionic gonadotropin/luteinizing hormone β subunit chimeras and mutants. Journal of Biological Chemistry, 265(15), 8511-8518.