Smelling sulfur

Proc. Natl Acad. Sci. USA 109, 3492–3497 (2012)

We all know that sulfurous compounds are smelly — think rotten eggs and food waste — and humans are very sensitive to them, being able to sense small volatile thiols down to 0.3 ppb. How they are detected, however, is not fully understood, but it has been suggested that metal ions could play a role. Now, a team led by Hiroaki Matsunami from Duke University Medical Centre, and Hanyi Zhuang from Shanghai Jiao Tong University, have shown that copper is essential for mice to be able to smell (methylthio)methanethiol (CH₃SCH₂SH; MTMT), a chemical in the urine of male mice that attracts females.

Matsunami, Zhuang and colleagues screened 219 mouse odorant receptor proteins to find those responsive to MTMT. To do this they measured the chemiluminescence of a luciferase reporter, which indirectly responded to the activation of odorant receptors. The receptor MOR244-3 responded strongly to MTMT and was therefore used subsequently to study the effects of metal ions on receptor activation. The addition of Cu²⁺ to the system increased the activation of MOR244-3 but this was not the case on addition of several other metal ions. The effect of Cu²⁺ was also confirmed by the addition of tetraethylenepentamine — a copper chelator that binds to and thus removes free Cu²⁺. This caused the receptor to stop responding, proving that copper is necessary for MTMT sensing.

Matsunami, Zhuang and colleagues also investigated a series of MTMT analogues and the effect of receptor mutations. The researchers suggest that the copper ions mediate the 'detection' process, by perhaps binding to the sulfurous ligands and altering their conformation, before they can both bind to the receptor.