2aew: Difference between revisions

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[[Image:2aew.jpg|left|200px]]
{{Seed}}
[[Image:2aew.png|left|200px]]


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{{STRUCTURE_2aew|  PDB=2aew  |  SCENE=  }}  
{{STRUCTURE_2aew|  PDB=2aew  |  SCENE=  }}  


'''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===




==Overview==
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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.
The line below this paragraph, {{ABSTRACT_PUBMED_16116438}}, adds the Publication Abstract to the page
(as it appears on PubMed at http://www.pubmed.gov), where 16116438 is the PubMed ID number.
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{{ABSTRACT_PUBMED_16116438}}


==About this Structure==
==About this Structure==
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[[Category: Hormone/growth factor]]
[[Category: Hormone/growth factor]]
[[Category: Mechanism]]
[[Category: Mechanism]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 18:57:49 2008''
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 16:21:40 2008''

Revision as of 13:21, 29 July 2008

File:2aew.png

Template:STRUCTURE 2aew

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

Template:ABSTRACT PUBMED 16116438

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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