2LMK

Solution Structure of Mouse Pheromone ESP1

2LMK の概要

• エントリーDOI: 10.2210/pdb2lmk/pdb
• 分子名称: Exocrine gland-secreting peptide 1 (1 entity in total)
• 機能のキーワード: pheromone, gpcr, signaling protein
• 由来する生物種: Mus musculus (mouse)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 6307.25

構造登録者

Yoshinaga, S.,Sato, T.,Hirakane, M.,Esaki, K.,Hamaguchi, T.,Haga-Yamanaka, S.,Tsunoda, M.,Kimoto, H.,Shimada, I.,Touhara, K.,Terasawa, H. (登録日: 2011-12-06, 公開日: 2013-04-17, 最終更新日: 2024-10-30)

主引用文献

Yoshinaga, S.,Sato, T.,Hirakane, M.,Esaki, K.,Hamaguchi, T.,Haga-Yamanaka, S.,Tsunoda, M.,Kimoto, H.,Shimada, I.,Touhara, K.,Terasawa, H.
Structure of the Mouse Sex Peptide Pheromone ESP1 Reveals a Molecular Basis for Specific Binding to the Class-C G-Protein-Coupled Vomeronasal Receptor
J.Biol.Chem., 2013

PubMed Abstract: Exocrine gland-secreting peptide 1 (ESP1) is a sex pheromone that is released in male mouse tear fluids and enhances female sexual receptive behavior. ESP1 is selectively recognized by a specific class C G-protein-coupled receptor (GPCR), V2Rp5, among the hundreds of receptors expressed in vomeronasal sensory neurons (VSNs). The specific sensing mechanism of the mammalian peptide pheromone by the class C GPCR remains to be elucidated. Here we identified the minimal functional region needed to retain VSN-stimulating activity in ESP1 and determined its three-dimensional structure, which adopts a helical fold stabilized by an intramolecular disulfide bridge with extensive charged patches. We then identified the amino acids involved in the activation of VSNs by a structure-based mutational analysis, revealing that the highly charged surface is crucial for the ESP1 activity. We also demonstrated that ESP1 specifically bound to an extracellular region of V2Rp5 by an in vitro pulldown assay. Based on homology modeling of V2Rp5 using the structure of the metabotropic glutamate receptor, we constructed a docking model of the ESP1-V2Rp5 complex in which the binding interface exhibited good electrostatic complementarity. These experimental results, supported by the molecular docking simulations, reveal that charge-charge interactions determine the specificity of ESP1 binding to V2Rp5 in the large extracellular region characteristic of class C GPCRs. The present study provides insights into the structural basis for the narrowly tuned sensing of mammalian peptide pheromones by class C GPCRs.

PubMed: 23576433
DOI: 10.1074/jbc.M112.436782

実験手法

SOLUTION NMR