Allosteric modulations in signal transduction of the melatonin receptor heterodimer MT1/MT2

The heterodimerization between melatonin type I (MT1) and type II (MT2) receptors has been well demonstrated by previous studies, However, the functional significance and the structure of the MT1/MT2 heterodimer remains largely unknown. This study characterized the functional interactions between MT1 and MT2 via the calcium mobilization and predicted the dimerization interface by computational modeling. Our study suggested that the activation of MT1/MT2 is gated by the MT1 protomer and provided structural insights of MT1/MT2 dimer, which facilitates the understanding of melatonin regulatory mechanisms and the potential therapeutic developments.