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Science 2 August 1991:
Vol. 253. no. 5019, pp. 545 - 548
DOI: 10.1126/science.1907025
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Articles

Science, Vol 253, Issue 5019, 545-548
Copyright © 1991 by American Association for the Advancement of Science

articles

Dimerization of human growth hormone by zinc

BC Cunningham, MG Mulkerrin, and JA Wells

Department of Protein Engineering, Genentech, South San Francisco, CA 94080.

Size-exclusion chromatography and sedimentation equilbrium studies demonstrated that zinc ion (Zn2+) induced the dimerization of human growth hormone (hGH). Scatchard analysis of 65Zn2+ binding to hGH showed that two Zn2+ ions associate per dimer of hGH in a cooperative fashion. Cobalt (II) can substitute for Zn2+ in the hormone dimer and gives a visible spectrum characteristic of cobalt coordinated in a tetrahedral fashion by oxygen- and nitrogen-containing ligands. Replacement of potential Zn2+ ligands (His18, His21, and Glu174) in hGH with alanine weakened both Zn2+ binding and hGH dimer formation. The Zn(2+)-hGH dimer was more stable than monomeric hGH to denaturation in guanidine-HCl. Formation of a Zn(2+)-hGH dimeric complex may be important for storage of hGH in secretory granules.


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