Biophysical characterization of GPCR oligomerization
Research output: Book/Report › Ph.D. thesis › Research
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Biophysical characterization of GPCR oligomerization. / Mathiasen, Signe.
Department of Chemistry, Faculty of Science, University of Copenhagen, 2013. 167 p.Research output: Book/Report › Ph.D. thesis › Research
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TY - BOOK
T1 - Biophysical characterization of GPCR oligomerization
AU - Mathiasen, Signe
PY - 2013
Y1 - 2013
N2 - The biophysical characterization of the fundamental molecular mechanisms behind G-protein coupled receptors (GPCRs) oligomerization is proposed to be paramount for understanding the pharmacological consequence of receptor self-association. Here we developed an in vitro assay that allowed a quantitative characterization of GPCR oligomerization. The assay provided the first quantification of the association energy of the β2 Adrenergic Receptor (β2AR), a prototypical GPCR. Furthermore we directly observed the time-dependent dimerization of β2AR and Cannabinoid receptor 1 at the single molecule level, and revealed the existence of several dimerization interfaces, each with specific kinetics. Finally we investigated how a property of themembrane solubilizing GPCRs affected oligomerization. We observed a dramatic decrease in oligomer stability with increasing geometrical membrane curvature. We anticipate that our assay will provide quantitative assessments of the functional and pharmacological consequences of GPCR oligomerization.
AB - The biophysical characterization of the fundamental molecular mechanisms behind G-protein coupled receptors (GPCRs) oligomerization is proposed to be paramount for understanding the pharmacological consequence of receptor self-association. Here we developed an in vitro assay that allowed a quantitative characterization of GPCR oligomerization. The assay provided the first quantification of the association energy of the β2 Adrenergic Receptor (β2AR), a prototypical GPCR. Furthermore we directly observed the time-dependent dimerization of β2AR and Cannabinoid receptor 1 at the single molecule level, and revealed the existence of several dimerization interfaces, each with specific kinetics. Finally we investigated how a property of themembrane solubilizing GPCRs affected oligomerization. We observed a dramatic decrease in oligomer stability with increasing geometrical membrane curvature. We anticipate that our assay will provide quantitative assessments of the functional and pharmacological consequences of GPCR oligomerization.
UR - https://soeg.kb.dk/permalink/45KBDK_KGL/fbp0ps/alma99121952792205763
M3 - Ph.D. thesis
BT - Biophysical characterization of GPCR oligomerization
PB - Department of Chemistry, Faculty of Science, University of Copenhagen
ER -
ID: 99363343