Engineering Salt Bridge Networks between Transmembrane Helices Confers Thermostability in G-Protein-Coupled Receptors.

ABSTRACT: Introduction of specific point mutations has been an effective strategy in enhancing the thermostability of G-protein-coupled receptors (GPCRs). Our previous work showed that a specific residue position on transmembrane helix 6 (TM6) in class A GPCRs consistently yields thermostable mutants. The crystal structure of human chemokine receptor CCR5 also showed increased thermostability upon mutation of two positions, A233D^6.33 and K303E^7.59. With the goal of testing the transferability of these two thermostabilizing mutations in other chemokine receptors, we tested the mutations A237D^6.33 and R307E^7.59 in human CCR3 for thermostability and aggregation properties in detergent solution. Interestingly, the double mutant exhibited a 6-10-fold decrease i

SUBMITTER: Ghosh S 

PROVIDER: S-EPMC6549507 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature