Allosteric Fingerprinting of G Protein-Coupled Receptor Monomers and Oligomers

Proposed research will exploit the exquisite sensitivity of allosteric interactions to conformational changes, to develop an enabling technology that can unambiguously fingerprint endogenously expressed G protein-coupled receptor (GPCR) complexes. The hypothesis is that GPCR monomers, dimers and higher order oligomers will have a unique profile of allosteric modulation, which in turn can be used to probe for GPCR interactions within healthy and disease tissue. The specific aims are: 1.To establish how the nature of the GPCR complex influences allosterism through systematic analysis of intramolecular and intermolecular allosteric interactions. 2.To fingerprint GPCR complexes within endogenous expression systems using allosteric profiling.