Multiscale spectroscopies for understanding GPCR mediated cell signalling

Anthony Watts
Biomembrane Structure Unit, Department of Biochemistry, University of Oxford
Tuesday, May 22, 2018 - 10:30am
CCBR Red Room
Invited Speaker Seminar
G protein-coupled receptors (GPCRs) play a pivotal role in cellular signalling, highlighted by the fact that they form the target for ~40% of marketed pharmaceuticals. While evidence has been accumulating for the existence and functional significance of GPCR oligomers, the matter is still under debate, in part due to lack of consensus on morphological aspects, such as the receptor interfaces involved in oligomerisation, and their possible dynamic nature [1]. Neurotensin receptor 1 (NTS1) is one of few GPCRs that can be produced in E. coli in an active state, and has been implicated in a variety of conditions including schizophrenia and various cancers. NTS1 has been demonstrated by us to show lipid dependent functionality [2-5] and dimerise in lipid bilayers [6], however, there is still no structural or dynamic information on the receptor dimer. Here, we combine ensemble FRET [6], DEER, single molecule methods and in silico approaches [7] to probe NTS1 dimerization. The results support the presence of a concentration-dependent dynamic equilibrium between monomers and dimers, which could provide a means of regulation of receptor signalling and biased coupling in vivo.
Dr. Oliver Ernst
BiophysTO Lunchtime Talks