2lmk | pdb_00002lmk

Solution Structure of Mouse Pheromone ESP1

spinqualitylabelsall models 2lmk, 20 NMR models Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2lmk is a 1 chain structure with sequence from Lk3 transgenic mice. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Gene: EG619517, ESP1, Gm6084 (LK3 transgenic mice) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed 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 VSNs-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 pull-down 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. Structure of the Mouse Sex Peptide Pheromone ESP1 Reveals a Molecular Basis for Specific Binding to the Class-C G-Protein-Coupled Vomeronasal Receptor.,Yoshinaga S, Sato T, Hirakane M, Esaki K, Hamaguchi T, Haga-Yamanaka S, Tsunoda M, Kimoto H, Shimada I, Touhara K, Terasawa H J Biol Chem. 2013 Apr 10. PMID:23576433 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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