Activating the prolactin receptor: Effect of the ligand on the conformation of the extracellular domain

Groothuizen, Flora S., Poger, David and Mark, Alan E. (2010) Activating the prolactin receptor: Effect of the ligand on the conformation of the extracellular domain. Journal of Chemical Theory and Computation, 6 10: 3274-3283. doi:10.1021/ct1003934


Author Groothuizen, Flora S.
Poger, David
Mark, Alan E.
Title Activating the prolactin receptor: Effect of the ligand on the conformation of the extracellular domain
Journal name Journal of Chemical Theory and Computation   Check publisher's open access policy
ISSN 1549-9618
1549-9626
Publication date 2010-10
Sub-type Article (original research)
DOI 10.1021/ct1003934
Volume 6
Issue 10
Start page 3274
End page 3283
Total pages 10
Place of publication Washington , D.C., U.S.A.
Publisher American Chemical Society
Collection year 2011
Language eng
Abstract The prolactin receptor resides on the surface of the cell as a preformed dimer. This suggests that cell signaling is triggered by conformational changes within the extracellular domain of the receptors. Here, by using atomistic molecular dynamics simulations, we show that the removal of the ligand placental lactogen from the dimeric form of the prolactin receptor results in a relative reorientation of the two extracellular domains by 20−30°, which corresponds to a clockwise rotation of the domains with respect to each other. Such a mechanism of activation for the prolactin receptor is similar to that proposed previously in the case of the growth hormone receptor. In addition to the effect of the removal of the ligand, the mechanical coupling between the extracellular and transmembrane domains within a model membrane was also examined. Copyright © 2010 American Chemical Society
Keyword Molecular-dynamics simulations
Growth-hormone receptor
Lactogenic hormones
Placental-lactogen
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
School of Chemistry and Molecular Biosciences
Institute for Molecular Bioscience - Publications
 
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Created: Sun, 31 Oct 2010, 00:08:59 EST