Turning the growth hormone receptor on: Evidence that hormone binding induces subunit rotation

Poger, David and Mark, Alan E. (2010) Turning the growth hormone receptor on: Evidence that hormone binding induces subunit rotation. Proteins: Structure, Function & Bioinformatics, 78 5: 1163-1174. doi:10.1002/prot.22636


Author Poger, David
Mark, Alan E.
Title Turning the growth hormone receptor on: Evidence that hormone binding induces subunit rotation
Journal name Proteins: Structure, Function & Bioinformatics   Check publisher's open access policy
ISSN 1097-0134
0887-3585
Publication date 2010-04-01
Year available 2009
Sub-type Article (original research)
DOI 10.1002/prot.22636
Volume 78
Issue 5
Start page 1163
End page 1174
Total pages 12
Place of publication New York, NY, United States
Publisher Wiley Interscience
Language eng
Formatted abstract
Atomistic molecular dynamics simulations have been used to investigate the conformational changes associated with the binding of human growth hormone (hGH) to the extracellular domains (ECD) of the human growth hormone receptor (hGHR), thereby shedding light on the mechanism of activation. It is shown that the removal of hGH from the hormone-bound receptor complex results in a counterclockwise rotation of the two subunits relative to each other by 30°-64° (average 45° ± 14°), in close agreement in terms of both the magnitude and direction of the rotation with that proposed based on mutagenesis experiments. In addition to providing evidence to support a rotational activation mechanism, the simulations have enabled the nature of the interaction interfaces in both the cytokine-bound and unliganded hGHR states to be analyzed in detail. © 2009 Wiley-Liss, Inc.
Keyword Cytokine receptor
Growth hormone
Molecular dynamics simulation
Receptor activation
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Available online 16 October 2009

 
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Created: Wed, 17 Feb 2010, 22:30:13 EST by Jennifer Falknau on behalf of School of Chemistry & Molecular Biosciences