The interplay of receptor dynamics and ligand residence time upon ligand efficacy at adenosine receptors
(C02)
Subject Area
Pharmacology
Cell Biology
Term
from 2015 to 2020
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 258780946
The molecular details leading to increased ligand residence time are currently insufficiently understood. The major question within this project will be to address conformational dynamic of a receptor in relation to ligand binding using FRET-microscopy with high kinetic resolution in living cells. Using adenosine receptors, we will: I) Study the role of the extracellular loop 2 in ligand binding kinetics; II) Compare the low ligand affinity A2B receptor to the high affinity A1 and A2A receptors; III) Investigate dynamic ligand binding in relation to the conformational dynamics of the H251A mutation at the A1 receptor; IV) Study the influence of G-proteins in receptor dynamics and receptor localization; V) Investigate the role of allosteric modulators in residence time and signaling using PD 81,723 as prototype; VI) Adapt the system to 96-well plates for faster throughput.
DFG Programme
CRC/Transregios
