Abstract
THE human pituitary hormones, growth hormone (hGH) and pro-lactin (hPRL), regulate a large variety of physiological processes, among which are growth and differentiation of muscle, bone and cartilage cells, and lactation1. These activities are initiated by hormone–receptor binding. The hGH and hPRL receptors (hGHR and hPHLR, respectively) are single-pass transmembrane receptors from class 1 of the haematopoietic receptor superfamily2,3. This classification is based on sequence similarity in their extracellular domains, notably a highly conserved pentapeptide, the so-called 'WSXWS box', the function of which is controversial. All ligands in class 1 activate their respective receptors by clustering mechanisms4. In the case of hGH, activation involves receptor homodimerization in a sequential process: the active ternary complex containing one ligand and two receptor molecules is formed by association of a receptor molecule to an intermediate 1:1 complex5–8. hPRL does not bind to the hGH receptor, but hGH binds to both the hGHR and hPRLR, and mutagenesis studies halve shown that the receptor-binding sites on hGH overlap9. We present here the crystal structure of the 1:1 complex of hGH bound to the extracellular domain of the hPRLR. Comparisons with the hGH–hGHR complex10 reveal how hGH can bind to the two distinctly different receptor binding surfaces.
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Somers, W., Ultsch, M., De Vos, A. et al. The X-ray structure of a growth hormone–prolactin receptor complex. Nature 372, 478–481 (1994). https://doi.org/10.1038/372478a0
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DOI: https://doi.org/10.1038/372478a0
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