Thermostabilisation of the serotonin transporter in a cocaine-bound conformation.

ABSTRACT: Structure determination of mammalian integral membrane proteins is challenging due to their instability upon detergent solubilisation and purification. Recent successes in the structure determination of G-protein-coupled receptors (GPCRs) resulted from the development of GPCR-specific protein engineering strategies. One of these, conformational thermostabilisation, could in theory facilitate structure determination of other membrane proteins by improving their tolerance to detergents and locking them in a specific conformation. We have therefore used this approach on the cocaine-sensitive rat serotonin transporter (SERT). Out of a panel of 554 point mutants throughout SERT, 10 were found to improve its thermostability. The most stabilising mutations were combined to make the thermostabilis

SUBMITTER: Abdul-Hussein S 

PROVIDER: S-EPMC3678023 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature