Dimerization of human growth hormone by zinc.
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.
Cunningham
B C
BC
Department of Protein Engineering, Genentech, South San Francisco, CA 94080.
Mulkerrin
M G
MG
Wells
J A
JA
D000595:Amino Acid Sequence; D001665:Binding Sites; D002850:Chromatography, Gel; D004492:Edetic Acid / Q000494:pharmacology; D013006:Growth Hormone / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D046911:Macromolecular Substances; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D011489:Protein Denaturation; D013053:Spectrophotometry; D015032:Zinc / Q000378:metabolism / Q000494:pharmacology*
D046911:Macromolecular Substances; D013006:Growth Hormone; D004492:Edetic Acid; D015032:Zinc