1BP3

THE XRAY STRUCTURE OF A GROWTH HORMONE-PROLACTIN RECEPTOR COMPLEX

Summary for 1BP3

• Entry DOI: 10.2210/pdb1bp3/pdb
• Descriptor: PROTEIN (GROWTH HORMONE), PROTEIN (PROLACTIN RECEPTOR), ZINC ION (3 entities in total)
• Functional Keywords: hormone, receptor, hormone/growth factor, hormone-growth factor complex
• Biological source: Homo sapiens (human); More
• Cellular location: Secreted: P01241; Membrane; Single-pass type I membrane protein. Isoform 7: Secreted: P16471
• Total number of polymer chains: 2
• Total formula weight: 46861.42

Authors

Somers, W.,Ultsch, M.,De Vos, A.M.,Kossiakoff, A.A. (deposition date: 1998-08-12, release date: 1998-08-19, Last modification date: 2023-08-09)

Primary citation

Somers, W.,Ultsch, M.,De Vos, A.M.,Kossiakoff, A.A.
The X-ray structure of a growth hormone-prolactin receptor complex.
Nature, 372:478-481, 1994

PubMed Abstract: The human pituitary hormones, growth hormone (hGH) and prolactin (hPRL), regulate a large variety of physiological processes, among which are growth and differentiation of muscle, bone and cartilage cells, and lactation. These activities are initiated by hormone-receptor binding. The hGH and hPRL receptors (hGHR and hPRLR, respectively) are single-pass transmembrane receptors from class 1 of the haematopoietic receptor superfamily. 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 mechanisms. 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 complex. hPRL does not bind to the hGH receptor, but hGH binds to both the hGHR and hPRLR, and mutagenesis studies have shown that the receptor-binding sites on hGH overlap. 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 complex reveal how hGH can bind to the two distinctly different receptor binding surfaces.

PubMed: 7984244
DOI: 10.1038/372478a0

Experimental method

X-RAY DIFFRACTION (2.9 Å)