Abstract
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 the
membrane 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.
membrane 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.
| Original language | English |
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| Publisher | Department of Chemistry, Faculty of Science, University of Copenhagen |
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| Number of pages | 167 |
| Publication status | Published - 2013 |