Conversion of human choriogonadotropin into a follitropin by protein engineering

Journal Article · Fri Feb 01 00:00:00 EST 1991 · Proceedings of the National Academy of Sciences of the United States of America; (United States)

DOI:https://doi.org/10.1073/pnas.88.3.760· OSTI ID:5043488

Campbell, R K; Dean-Emig, D M; Moyle, W R ^[1]

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1. Univ. of Medicine and Dentistry of New Jersey, Piscataway (United States)

Human reproduction is dependent upon the action of follicle-stimulating hormone (hFSH), luteinizing hormone (hLH), and chorionic gonadotropin (hCG). While the {alpha} subunits of these heterodimeric proteins can be interchanged without effect on receptor-binding specificity, their {beta} subunits differ and direct hormone binding to either LH/CG or FSH receptors. Previous studies employing chemical modifications of the hormones, monoclonal antibodies, or synthetic peptides have implicated hCG {beta}-subunit residues between Cys-38 and Cys-57 and corresponding regions of hLH{beta} and hFSH{beta} in receptor recognition and activation. Since the {beta} subunits of hCG or hLH and hFSH exhibit very little sequence similarity in this region, the authors postulated that these residues might contribute to hormone specificity. To test this hypothesis the authors constructed chimeric hCG/hFSH {beta} subunits, coexpressed them with the human {alpha} subunit, and examined their ability to interact with LH and FSH receptors and hormone-specific monoclonal antibodies. Surprisingly, substitution of hFSH{beta} residues 33-52 for hCG{beta} residues 39-58 had no effect on receptor binding or stimulation. However, substitution of hFSH{beta} residues 88-108 in place of the carboxyl terminus of hCG{beta} (residues 94-145) resulted in a hormone analog identical to hFSH in its ability to bind and stimulate FSH receptors. The altered binding specificity displayed by this analog is not attributable solely to the replacement of hCG{beta} residues 108-145 or substitution of residues in the determinant loop located between hCD{beta} residues 93 and 100.

• OSTI ID: 5043488
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (United States), Vol. 88:3; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
GONADOTROPINS
GENETIC ENGINEERING
PEPTIDE HORMONES
AMINO ACID SEQUENCE
DOSE-RESPONSE RELATIONSHIPS
FSH
IMMUNOLOGY
IODINE 125
LH
MONOCLONAL ANTIBODIES
PLASMIDS
REPRODUCTION
TESTOSTERONE
ANDROGENS
ANDROSTANES
ANTIBODIES
BETA DECAY RADIOISOTOPES
BIOTECHNOLOGY
CELL CONSTITUENTS
DAYS LIVING RADIOISOTOPES
ELECTRON CAPTURE RADIOISOTOPES
HORMONES
HYDROXY COMPOUNDS
INTERMEDIATE MASS NUCLEI
INTERNAL CONVERSION RADIOISOTOPES
IODINE ISOTOPES
ISOTOPES
KETONES
MOLECULAR STRUCTURE
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
PITUITARY HORMONES
PROTEINS
RADIOISOTOPES
STEROID HORMONES
STEROIDS
550201* - Biochemistry- Tracer Techniques