Figure 4. Allosteric modulation of the 5-HT₃A receptor through chemical modification of engineered cysteines in the vestibule site.

(a) Example traces of agonist-evoked channel responses of the L151C 5-HT_3AR mutant before and after modification with MTSEA-biotin show potentiation after cysteine modification. (b) Location of L151C and other engineered cysteine mutants in this study, shown in ball and stick representation. (c) Concentration-activation curves before and after modification with MTSEA-biotin are a Hill curve fit for the recordings shown in (a) as well as additional data for T112C (d) and K149C. (c–e) Each of these three mutants reveal a leftward shift of the curve upon cysteine modification, consistent with a positive allosteric effect. In the case of L151C, this effect is combined with a large increase of the maximal current response.