Full rescue of an inactive olfactory receptor mutant by elimination of an allosteric ligand-gating site.

ABSTRACT: Ligand-gating has recently been proposed as a novel mechanism to regulate olfactory receptor sensitivity. TAAR13c, the zebrafish olfactory receptor activated by the death-associated odor cadaverine, appears to possess an allosteric binding site for cadaverine, which was assumed to block progress of the ligand towards the internal orthosteric binding-and-activation site. Here we have challenged the suggested gating mechanism by modeling the entry tunnel for the ligand as well as the ligand path inside the receptor. We report an entry tunnel, whose opening is blocked by occupation of the external binding site by cadaverine, confirming the hypothesized gating mechanism. A multistep docking algorithm suggested a plausible path for cadaverine from the allosteric to the orthosteric binding-and-a

SUBMITTER: Sharma K 

PROVIDER: S-EPMC6018111 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature