1bp3: Difference between revisions

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|PDB= 1bp3 |SIZE=350|CAPTION= <scene name='initialview01'>1bp3</scene>, resolution 2.90&Aring;
|PDB= 1bp3 |SIZE=350|CAPTION= <scene name='initialview01'>1bp3</scene>, resolution 2.90&Aring;
|SITE=  
|SITE=  
|LIGAND= <scene name='pdbligand=ZN:ZINC ION'>ZN</scene>
|LIGAND= <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>
|ACTIVITY=  
|ACTIVITY=  
|GENE=  
|GENE=  
|DOMAIN=
|RELATEDENTRY=
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1bp3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1bp3 OCA], [http://www.ebi.ac.uk/pdbsum/1bp3 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1bp3 RCSB]</span>
}}
}}


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==Overview==
==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.
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:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=139250 139250]], Growth hormone deficiency, isolated, type IA OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=139250 139250]], Growth hormone deficiency, isolated, type IB OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=139250 139250]], Growth hormone deficiency, isolated, type II OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=139250 139250]], Kowarski syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=139250 139250]], Short stature, familial OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=139250 139250]]


==About this Structure==
==About this Structure==
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[[Category: Ultsch, M.]]
[[Category: Ultsch, M.]]
[[Category: Vos, A M.De.]]
[[Category: Vos, A M.De.]]
[[Category: ZN]]
[[Category: hormone]]
[[Category: hormone]]
[[Category: hormone/growth factor]]
[[Category: hormone/growth factor]]
[[Category: receptor]]
[[Category: receptor]]


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