Structural elucidation of ETHR-A and ETHR-B from Plutella xylostella and insight into non-conservative mutations in transmembrane helix-6.

The development of Diamondback moth (DBM) depends on the ecdysis triggering hormone receptor (ETHR); a neuronal membrane G-protein coupled receptor (GPCR) connected to the metamorphosis cascade. Lepidopteran insect DBM is an infamous pest of cruciferous plants. This study examined the full-length coding sequences (CDS) of ETHR-A and ETHR-B from the DBM genome. The three-dimensional (3 D) models of both receptors were generated in an inactive state. The behaviour and stability of receptors were examined using molecular dynamics simulations in a lipid membrane system for 300 ns and established a GPCR family-based view. Secondary interactions within receptors were studied to know more about factors contributing to their stability. Multiple sequence alignment revealed conserved features of insect ETHRs those compared to the GPCR family proteins. These features were helpful during the evaluation of the molecular models of both receptors. Side-chain orientation of conserved residues, non-conserved and conserved hydrogen-bond networks (HBN) and hydrophobic clusters were examined in the structures of both receptors. The non-conserved residues L6.35, T6.39, C/S6.43, and L6.48, are present in a conserved position on the transmembrane helix-6 (TM6) of ETHRs. In TM6, ETHR-A and ETHR-B differ at positions C/S6.43 and Y/F6.51, both being part of the HBN.Communicated by Ramaswamy H. Sarma.