2aew
From Proteopedia
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| , resolution 2.700Å | |||||||
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| Coordinates: | save as pdb, mmCIF, xml | ||||||
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
Page seeded by OCA on Thu Mar 20 15:48:52 2008
