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JCS ePress online publication date 4 Jul 2006
doi: 10.1242/jcs.03036

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Research Article

Disulfide bonds determine growth hormone receptor folding, dimerisation and ligand binding


Monique J.M. van den Eijnden, Liza L. Lahaye, and Ger J. Strous*
* Author for correspondence (e-mail: strous{at}med.uu.nl)

The growth hormone receptor contains seven cysteine residues in its extracellular domain. The six in the growth hormone binding domain form disulfide bonds, and help the receptor to gain its correct three-dimensional structure. In this study we replaced the cysteine for serine and alanine residues and investigated their role in growth hormone receptor folding, dimerisation and signal transduction. Folding and growth hormone binding capacity of the wild-type growth hormone receptor require less than two minutes for completion. Although less efficient, all mutant receptors arrive at the cell surface as pre-formed dimers. Disulfide bond C38-C48 is important for efficient maturation. The middle disulfide-bond, C83-C94, is important for ligand binding. Removing disulfide bond C108-C122 has little effect without affecting signalling. When two or all disulfide bonds are changed, ligand binding and activation are blocked. Dimerisation is delayed when all disulfide bonds are destroyed.


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© The Company of Biologists Ltd 2006