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J Biol Chem

Title:		An ionic lock and a hydrophobic zipper mediate the coupling between an insect pheromone receptor BmOR3 and downstream effectors
Author(s):		Lin JY; Yang Z; Yang C; Du JX; Yang F; Cheng J; Pan W; Zhang SJ; Yan X; Wang J; Wang J; Tie L; Yu X; Chen X; Sun JP;
Address:		"Key Laboratory Experimental Teratology of the Ministry of Education and Department of Physiology, School of Basic Medical Sciences, Shandong University, Jinan, China. Key Laboratory Experimental Teratology of the Ministry of Education and Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Shandong University, Jinan, China. Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, China. Department of Pharmacology, School of Basic Medical Sciences, Shandong University, Jinan, China. Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, China. Key Laboratory Experimental Teratology of the Ministry of Education and Department of Physiology, School of Basic Medical Sciences, Shandong University, Jinan, China. Electronic address: yuxiao@sdu.edu.cn. Department of Medicinal Chemistry, School of Pharmaceutical Engineering and Life Science, Changzhou University, Changzhou, Jiangsu, China. Electronic address: xinchen@cczu.edu.cn. Key Laboratory Experimental Teratology of the Ministry of Education and Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Shandong University, Jinan, China; Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, China. Electronic address: sunjinpeng@sdu.edu.cn"
Journal Title:		J Biol Chem
Year:		2021
Volume:		20210902
Issue:		4
Page Number:		101160 -
DOI:		10.1016/j.jbc.2021.101160
ISSN/ISBN:		1083-351X (Electronic) 0021-9258 (Print) 0021-9258 (Linking)
Abstract:		"Pheromone receptors (PRs) recognize specific pheromone compounds to guide the behavioral outputs of insects, which are the most diverse group of animals on earth. The activation of PRs is known to couple to the calcium permeability of their coreceptor (Orco) or putatively with G proteins; however, the underlying mechanisms of this process are not yet fully understood. Moreover, whether this transverse seven transmembrane domain (7TM)-containing receptor is able to couple to arrestin, a common effector for many conventional 7TM receptors, is unknown. Herein, using the PR BmOR3 from the silk moth Bombyx mori and its coreceptor BmOrco as a template, we revealed that an agonist-induced conformational change of BmOR3 was transmitted to BmOrco through transmembrane segment 7 from both receptors, resulting in the activation of BmOrco. Key interactions, including an ionic lock and a hydrophobic zipper, are essential in mediating the functional coupling between BmOR3 and BmOrco. BmOR3 also selectively coupled with Gi proteins, which was dispensable for BmOrco coupling. Moreover, we demonstrated that trans-7TM BmOR3 recruited arrestin in an agonist-dependent manner, which indicates an important role for BmOR3-BmOrco complex formation in ionotropic functions. Collectively, our study identified the coupling of G protein and arrestin to a prototype trans-7TM PR, BmOR3, and provided important mechanistic insights into the coupling of active PRs to their downstream effectors, including coreceptors, G proteins, and arrestin"
Keywords:		"Animals *Bombyx/chemistry/genetics/metabolism HEK293 Cells Humans Hydrophobic and Hydrophilic Interactions *Insect Proteins/chemistry/genetics/metabolism Protein Domains *Receptors, Odorant/chemistry/genetics/metabolism BmOR3 BmOrco Bombyx mori G protein;"
Notes:		"MedlineLin, Jing-Yu Yang, Zhao Yang, Chan Du, Ji-Xiang Yang, Fan Cheng, Jie Pan, Wei Zhang, Shi-Jie Yan, Xu Wang, Jia Wang, Jin Tie, Lu Yu, Xiao Chen, Xin Sun, Jin-Peng eng Research Support, Non-U.S. Gov't 2021/09/05 J Biol Chem. 2021 Oct; 297(4):101160. doi: 10.1016/j.jbc.2021.101160. Epub 2021 Sep 2"