# Phylogenetic and Structural Insights into Melatonin Receptors in Plants: Case Study in Capsicum chinense Jacq

## TL;DR

This paper explores the structure and function of melatonin receptors in plants, focusing on their phylogeny and binding properties in Capsicum chinense.

## Contribution

The study identifies a conserved internal melatonin-binding site in plant melatonin receptors and provides structural insights into their function.

## Key findings

- Phylogenetic analysis shows an expansion of melatonin receptor homologs in angiosperms grouped into three clades.
- Docking studies reveal a conserved internal melatonin-binding site with stronger binding affinity than a superficial pocket.
- Hydrophobic interactions and hydrogen bonds are key in melatonin binding, with transport simulations showing favorable movement through the internal cavity.

## Abstract

Recently, it has been proposed that plant melatonin receptors belong to the superfamily of G protein-coupled receptors (GPCRs). However, a detailed description of the phylogeny, protein structure, and binding properties of melatonin, which is still lacking, can help determine the signaling and function of this compound. Melatonin receptor homologs (PMTRs) were identified in 90 Viridiplantae sensu lato proteomes using profile Hidden Markov Models (HMM), which yielded 174 receptors across 87 species. Phylogenetic analysis revealed an expansion of PMTR sequences in angiosperms, which were grouped into three clades. Docking studies uncovered a conserved internal melatonin-binding site in PMTRs, which was analogous to the site in human MT1 receptors. Binding affinity simulations indicated this internal site exhibits stronger melatonin binding compared to a previously reported superficial pocket. Ligand–receptor interaction analysis and alanine scanning highlighted a major role of hydrophobic interactions, with hydrogen bonds contributing predominantly at the internal site, while non-interacting charged residues stabilize the binding pocket. Tunnel and ligand transport simulations suggested melatonin moves favorably through the internal cavity to access the binding site. Also, we presented for the first time details of these pockets in a non-model species, Capsicum chinense. Taken together, the structural analyses presented here illustrate opportunities and theoretical evidence for performing structure–function studies via mutations in specific residues within the proposed new melatonin-binding site in PMTRs, shedding light on their role in plant melatonin signaling.