Zinc mediation of the binding of human growth hormone to the human prolactin receptor

Journal Article · Fri Dec 21 00:00:00 EST 1990 · Science (Washington, D.C.); (United States)

DOI:https://doi.org/10.1126/science.2270485· OSTI ID:5696772

Cunningham, B C; Bass, S; Fuh, G; Wells, J A ^[1]

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1. Genentech, Inc., San Francisco, CA (United States)

Human growth hormone (hGH) elicits a diverse set of biological activities including lactation that derives from binding to the prolactin (PRL) receptor. The binding affinity of hGH for the extracellular binding domain of the hPRL receptor (hPRLbp) was increased about 8,000-fold by addition of 50 micromolar ZnCl{sub 2}. Zinc was not required for binding of hGH to the hGH binding protein (hGHbp) or for binding of hPRL to the hPRLbp. Other divalent metal ions (Ca{sup 2+}, Mg{sup 2+}, Cu{sup 2+}, Mn{sup 2+}, and Co{sup 2+}) at physiological concentrations did not support such strong binding. Scatchard analysis indicated a stoichiometry of one Zn{sup 2+} per hGH{center dot}hPRLbp complex. Mutational analysis showed that a cluster of three residues (His{sup 18}, His{sup 21}, and Glu{sup 174}) in hGH and His{sup 188} from the hPRLbp (conserved in all PRL receptors but not GH receptors) are probable Zn{sup 2+} ligands. This polypeptide hormone{center dot}receptor zinc sandwich provides a molecular mechanism to explain why nonprimate GHs are not lactogenic and offers a molecular link between zinc deficiency and its association with altered functions of hGH.

• OSTI ID: 5696772
• Journal Information: Science (Washington, D.C.); (United States), Vol. 250:4988; ISSN 0036-8075
• Country of Publication: United States
• Language: English

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