2aew
From Proteopedia
(New page: 200px<br /> <applet load="2aew" size="450" color="white" frame="true" align="right" spinBox="true" caption="2aew, resolution 2.700Å" /> '''A model for growth...) |
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'''A model for growth hormone receptor activation based on subunit rotation within a receptor dimer'''<br /> | '''A model for growth hormone receptor activation based on subunit rotation within a receptor dimer'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2AEW is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | + | 2AEW is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AEW OCA]. |
==Reference== | ==Reference== | ||
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[[Category: mechanism]] | [[Category: mechanism]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 17:14:30 2008'' |
Revision as of 15:14, 15 February 2008
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A model for growth hormone receptor activation based on subunit rotation within a receptor dimer
Contents |
Overview
Growth hormone is believed to activate the growth hormone receptor (GHR), by dimerizing two identical receptor subunits, leading to activation of, JAK2 kinase associated with the cytoplasmic domain. However, we have, reported previously that dimerization alone is insufficient to activate, full-length GHR. By comparing the crystal structure of the liganded and, unliganded human GHR extracellular domain, we show here that there is no, substantial change in its conformation on ligand binding. However, the, receptor can be activated by rotation without ligand by inserting a, defined number of alanine residues within the transmembrane domain., Fluorescence resonance energy transfer (FRET), bioluminescence resonance, energy transfer (BRET) and coimmunoprecipitation studies suggest that, receptor subunits undergo specific transmembrane interactions independent, of hormone binding. We propose an activation mechanism involving a, relative rotation of subunits within a dimeric receptor as a result of, asymmetric placement of the receptor-binding sites on the ligand.
Disease
Known diseases associated with this structure: Increased responsiveness to growth hormone OMIM:[600946], Laron dwarfism OMIM:[600946], Short stature, autosomal dominant, with normal serum growth hormone binding protein OMIM:[600946], Short stature, idiopathic OMIM:[600946]
About this Structure
2AEW is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Model for growth hormone receptor activation based on subunit rotation within a receptor dimer., Brown RJ, Adams JJ, Pelekanos RA, Wan Y, McKinstry WJ, Palethorpe K, Seeber RM, Monks TA, Eidne KA, Parker MW, Waters MJ, Nat Struct Mol Biol. 2005 Sep;12(9):814-21. Epub 2005 Aug 21. PMID:16116438
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