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 -