1bp3

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spinqualitylabelsall models 1bp3, resolution 2.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

THE XRAY STRUCTURE OF A GROWTH HORMONE-PROLACTIN RECEPTOR COMPLEX

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

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.

Disease

Known diseases associated with this structure: Growth hormone deficiency OMIM:[139250], Growth hormone deficiency, isolated, type IA OMIM:[139250], Growth hormone deficiency, isolated, type IB OMIM:[139250], Growth hormone deficiency, isolated, type II OMIM:[139250], Kowarski syndrome OMIM:[139250], Short stature, familial OMIM:[139250]

About this Structure

1BP3 is a Protein complex structure of sequences from Homo sapiens with as ligand. Full crystallographic information is available from OCA.

Reference

The X-ray structure of a growth hormone-prolactin receptor complex., Somers W, Ultsch M, De Vos AM, Kossiakoff AA, Nature. 1994 Dec 1;372(6505):478-81. PMID:7984244

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