2aew

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[[Image:2aew.jpg|left|200px]]
[[Image:2aew.jpg|left|200px]]
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{{Structure
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|PDB= 2aew |SIZE=350|CAPTION= <scene name='initialview01'>2aew</scene>, resolution 2.700&Aring;
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The line below this paragraph, containing "STRUCTURE_2aew", creates the "Structure Box" on the page.
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{{STRUCTURE_2aew| PDB=2aew | SCENE= }}
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2aew FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2aew OCA], [http://www.ebi.ac.uk/pdbsum/2aew PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2aew RCSB]</span>
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'''A model for growth hormone receptor activation based on subunit rotation within a receptor dimer'''
'''A model for growth hormone receptor activation based on subunit rotation within a receptor dimer'''
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[[Category: Parker, M W.]]
[[Category: Parker, M W.]]
[[Category: Waters, M J.]]
[[Category: Waters, M J.]]
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[[Category: hormone/growth factor]]
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[[Category: Hormone/growth factor]]
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[[Category: mechanism]]
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[[Category: Mechanism]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 18:57:49 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:51:41 2008''
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Revision as of 15:57, 3 May 2008

Template:STRUCTURE 2aew

A model for growth hormone receptor activation based on subunit rotation within a receptor dimer


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.

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 Sat May 3 18:57:49 2008

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