Phylogenetic and Structural Insights into Melatonin Receptors in Plants: Case Study in <i>Capsicum chinense</i> Jacq

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 funct...

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Main Authors: Adrian Toledo-Castiñeira, Mario E. Valdés-Tresanco, Georgina Estrada-Tapia, Miriam Monforte-González, Manuel Martínez-Estévez, Ileana Echevarría-Machado
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Plants
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Online Access:https://www.mdpi.com/2223-7747/14/13/1952
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author Adrian Toledo-Castiñeira
Mario E. Valdés-Tresanco
Georgina Estrada-Tapia
Miriam Monforte-González
Manuel Martínez-Estévez
Ileana Echevarría-Machado
author_facet Adrian Toledo-Castiñeira
Mario E. Valdés-Tresanco
Georgina Estrada-Tapia
Miriam Monforte-González
Manuel Martínez-Estévez
Ileana Echevarría-Machado
author_sort Adrian Toledo-Castiñeira
collection DOAJ
description 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, <i>Capsicum chinense</i>. 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.
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spelling doaj-art-a8cd5de8590d4e08b2212299cc33d2df2025-08-20T02:36:34ZengMDPI AGPlants2223-77472025-06-011413195210.3390/plants14131952Phylogenetic and Structural Insights into Melatonin Receptors in Plants: Case Study in <i>Capsicum chinense</i> JacqAdrian Toledo-Castiñeira0Mario E. Valdés-Tresanco1Georgina Estrada-Tapia2Miriam Monforte-González3Manuel Martínez-Estévez4Ileana Echevarría-Machado5Unidad de Biología Integrativa, Centro de Investigación Científica de Yucatán (CICY), Calle 43 No. 130, Mérida CP 97205, MexicoCentre for Molecular Simulations, University of Calgary, Calgary, AB T2N 1N4, CanadaUnidad de Biología Integrativa, Centro de Investigación Científica de Yucatán (CICY), Calle 43 No. 130, Mérida CP 97205, MexicoUnidad de Biología Integrativa, Centro de Investigación Científica de Yucatán (CICY), Calle 43 No. 130, Mérida CP 97205, MexicoUnidad de Biología Integrativa, Centro de Investigación Científica de Yucatán (CICY), Calle 43 No. 130, Mérida CP 97205, MexicoUnidad de Biología Integrativa, Centro de Investigación Científica de Yucatán (CICY), Calle 43 No. 130, Mérida CP 97205, MexicoRecently, 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, <i>Capsicum chinense</i>. 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.https://www.mdpi.com/2223-7747/14/13/1952melatoninphytomelatonin receptor PMTRG protein-coupled receptorphylogenyHMMmolecular docking
spellingShingle Adrian Toledo-Castiñeira
Mario E. Valdés-Tresanco
Georgina Estrada-Tapia
Miriam Monforte-González
Manuel Martínez-Estévez
Ileana Echevarría-Machado
Phylogenetic and Structural Insights into Melatonin Receptors in Plants: Case Study in <i>Capsicum chinense</i> Jacq
Plants
melatonin
phytomelatonin receptor PMTR
G protein-coupled receptor
phylogeny
HMM
molecular docking
title Phylogenetic and Structural Insights into Melatonin Receptors in Plants: Case Study in <i>Capsicum chinense</i> Jacq
title_full Phylogenetic and Structural Insights into Melatonin Receptors in Plants: Case Study in <i>Capsicum chinense</i> Jacq
title_fullStr Phylogenetic and Structural Insights into Melatonin Receptors in Plants: Case Study in <i>Capsicum chinense</i> Jacq
title_full_unstemmed Phylogenetic and Structural Insights into Melatonin Receptors in Plants: Case Study in <i>Capsicum chinense</i> Jacq
title_short Phylogenetic and Structural Insights into Melatonin Receptors in Plants: Case Study in <i>Capsicum chinense</i> Jacq
title_sort phylogenetic and structural insights into melatonin receptors in plants case study in i capsicum chinense i jacq
topic melatonin
phytomelatonin receptor PMTR
G protein-coupled receptor
phylogeny
HMM
molecular docking
url https://www.mdpi.com/2223-7747/14/13/1952
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