Relax, Cool Down and Scaffold: How to Restore Surface Expression of Folding-Deficient Mutant GPCRs and SLC6 Transporters.

ABSTRACT: Many diseases arise from mutations, which impair protein folding. The study of folding-deficient variants of G protein-coupled receptors and solute carrier 6 (SLC6) transporters has shed light on the folding trajectory, how it is monitored and how misfolding can be remedied. Reducing the temperature lowers the energy barrier between folding intermediates and thereby eliminates stalling along the folding trajectory. For obvious reasons, cooling down is not a therapeutic option. One approach to rescue misfolded variants is to use membrane-permeable orthosteric ligands. Antagonists of GPCRs are-in many instances-effective pharmacochaperones: they restore cell surface expression provided that they enter cells and bind to folding intermediates. Pharmacochaperoning of SLC6 transporters is less r

SUBMITTER: Asjad HMM 

PROVIDER: S-EPMC5713384 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature