1bp3
THE XRAY STRUCTURE OF A GROWTH HORMONE-PROLACTIN RECEPTOR COMPLEX
Structural highlights
DiseaseSOMA_HUMAN Defects in GH1 are a cause of growth hormone deficiency isolated type 1A (IGHD1A) [MIM:262400; also known as pituitary dwarfism I. IGHD1A is an autosomal recessive deficiency of GH which causes short stature. IGHD1A patients have an absence of GH with severe dwarfism and often develop anti-GH antibodies when given exogenous GH.[1] Defects in GH1 are a cause of growth hormone deficiency isolated type 1B (IGHD1B) [MIM:612781; also known as dwarfism of Sindh. IGHD1B is an autosomal recessive deficiency of GH which causes short stature. IGHD1B patients have low but detectable levels of GH. Dwarfism is less severe than in IGHD1A and patients usually respond well to exogenous GH. Defects in GH1 are the cause of Kowarski syndrome (KWKS) [MIM:262650; also known as pituitary dwarfism VI.[2] [3] [4] Defects in GH1 are a cause of growth hormone deficiency isolated type 2 (IGHD2) [MIM:173100. IGHD2 is an autosomal dominant deficiency of GH which causes short stature. Clinical severity is variable. Patients have a positive response and immunologic tolerance to growth hormone therapy. FunctionSOMA_HUMAN Plays an important role in growth control. Its major role in stimulating body growth is to stimulate the liver and other tissues to secrete IGF-1. It stimulates both the differentiation and proliferation of myoblasts. It also stimulates amino acid uptake and protein synthesis in muscle and other tissues. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe 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. 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[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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