Activating and inactivating mutations in numerous human G protein-coupled receptors(GPCRs)are associated with a wide range of disease phenotypes.Here we use several class A GPCRs with a particularly large set of ident...Activating and inactivating mutations in numerous human G protein-coupled receptors(GPCRs)are associated with a wide range of disease phenotypes.Here we use several class A GPCRs with a particularly large set of identified disease-associated mutations,many of which were biochemically characterized,along with known GPCR structures and current models of GPCR activation,to understand the molecular mechanisms yielding pathological phenotypes.Based on this mechanistic understanding we also propose different therapeutic approaches,both conventional,using small molecule ligands,and novel,involving gene therapy.展开更多
基金This work was supported by NIH grants GM077561,EY011500,and GM109955(VVG)and DAAD RISE worldwide summer scholarship and Eberhard Karls Universitat Tubingen(Germany)Master’s program(HS).
文摘Activating and inactivating mutations in numerous human G protein-coupled receptors(GPCRs)are associated with a wide range of disease phenotypes.Here we use several class A GPCRs with a particularly large set of identified disease-associated mutations,many of which were biochemically characterized,along with known GPCR structures and current models of GPCR activation,to understand the molecular mechanisms yielding pathological phenotypes.Based on this mechanistic understanding we also propose different therapeutic approaches,both conventional,using small molecule ligands,and novel,involving gene therapy.
