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  2. 上海药物研究所
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  4. 新药研究国家重点实验室
Molecular insights into the activation mechanism of GPR156 in maintaining auditory function

文献类型：期刊论文

作者Ma, Xiangyu3; Chen, Li-Nan2,4,5; Liao, Menghui3; Zhang, Liyan3; Xi, Kun2,4; Guo, Jiamin3; Shen, Cangsong6,7; Shen, Dan-Dan2,4,5; Cai, Pengjun8; Shen, Qingya5
刊名NATURE COMMUNICATIONS
出版日期2024-12-05
卷号15期号:1页码:16
DOI10.1038/s41467-024-54681-5
英文摘要The class C orphan G-protein-coupled receptor (GPCR) GPR156, which lacks the large extracellular region, plays a pivotal role in auditory function through Gi2/3. Here, we firstly demonstrate that GPR156 with high constitutive activity is essential for maintaining auditory function, and further reveal the structural basis of the sustained role of GPR156. We present the cryo-EM structures of human apo GPR156 and the GPR156-Gi3 complex, unveiling a small extracellular region formed by extracellular loop 2 (ECL2) and the N-terminus. The GPR156 dimer in both apo state and Gi3 protein-coupled state adopt a transmembrane (TM)5/6-TM5/6 interface, indicating the high constitutive activity of GPR156 in the apo state. Furthermore, C-terminus in G-bound subunit of GPR156 plays a dual role in promoting G protein binding within G-bound subunit while preventing the G-free subunit from binding to additional G protein. Together, these results explain how GPR156 constitutive activity is maintained through dimerization and provide a mechanistic insight into the sustained role of GPR156 in maintaining auditory function.
WOS关键词PARTICLE MESH EWALD ; CRYO-EM STRUCTURE ; LIGAND RECOGNITION ; PROTEIN
资助项目the National Key Research and Development Program of China (2021YFA1101300 (R.C.), 2021YFA1101800 (R.C.) and 2020YFA0112503 (R.C.)) ; the STI2030-Major Projects (2022ZD0205400 (R.C.)) ; the National Natural Science Foundation of China (82330033 (R.C.), 82030 ; Zhejiang University[2021ZD0203304] ; STI2030-Major Projects[2023YFC2508402] ; STI2030-Major Projects[2021YFA1101300] ; STI2030-Major Projects[2021YFA1101800] ; STI2030-Major Projects[2020YFA0113600] ; STI2030-Major Projects[2020YFA0112503] ; National Key Research and Development Program of China ; Fundamental Research Funds for the Central Universities[LR22C050002] ; Fundamental Research Funds for the Central Universities[2022ZD0205400] ; Zhejiang Province Natural Science Fund for Excellent Young Scholars[82330033] ; Zhejiang Province Natural Science Fund for Excellent Young Scholars[82030029] ; Zhejiang Province Natural Science Fund for Excellent Young Scholars[92149304] ; Zhejiang Province Natural Science Fund for Excellent Young Scholars[82371162] ; Zhejiang Province Natural Science Fund for Excellent Young Scholars[32430051] ; Zhejiang Province Natural Science Fund for Excellent Young Scholars[92353303] ; Zhejiang Province Natural Science Fund for Excellent Young Scholars[32141004] ; Zhejiang Province Natural Science Fund for Excellent Young Scholars[32330049] ; Zhejiang Province Natural Science Fund for Excellent Young Scholars[82320108021] ; Zhejiang Province Natural Science Fund for Excellent Young Scholars[32300598] ; Zhejiang Province Natural Science Fund for Excellent Young Scholars[32371249] ; Zhejiang Province Natural Science Fund for Excellent Young Scholars[32100959] ; Zhejiang Province Natural Science Fund for Excellent Young Scholars[82322070] ; Zhejiang Province Natural Science Fund for Excellent Young Scholars[U23A200440] ; Zhejiang Province Natural Science Fund for Excellent Young Scholars[82401369] ; Zhejiang Province Natural Science Fund for Excellent Young Scholars[82401375] ; National Natural Science Foundation of China[2019YFA0508800] ; National Natural Science Foundation of China[2023YFC2306800] ; Ministry of Science and Technology[2021C03039] ; Key R&D Projects of Zhejiang Province[2020R01006] ; Key R&D Projects of Zhejiang Province[2024C03147] ; Leading Innovative and Entrepreneur Team Introduction Program of Zhejiang[2023TQ0056] ; Leading Innovative and Entrepreneur Team Introduction Program of Zhejiang[2023M730575] ; Leading Innovative and Entrepreneur Team Introduction Program of Zhejiang[GZC20230435] ; Leading Innovative and Entrepreneur Team Introduction Program of Zhejiang[2024M750455] ; Leading Innovative and Entrepreneur Team Introduction Program of Zhejiang[GZB20240145] ; China Postdoctoral Science Foundation[BK20232007] ; China Postdoctoral Science Foundation[BK20241692] ; Natural Science Foundation of Jiangsu Province[BK20233002] ; Jiangsu Provincial Scientific Research Center of Applied Mathematics[GZNL2023A03007] ; Major Project of Guangzhou National Laboratory[JCYJ20210324125608022] ; Shenzhen Science and Technology Program[YKY-KF202201] ; Guangdong Academy of Medical Sciences[Z200019] ; Beijing Natural Science Foundation[RF1028623028] ; Start-up Research Fund of Southeast University
WOS研究方向Science & Technology - Other Topics
WOS记录号WOS:001372601000017
出版者NATURE PORTFOLIO
源URL[http://119.78.100.183/handle/2S10ELR8/315043]  
专题新药研究国家重点实验室
通讯作者Liu, Jianfeng; Mao, Chunyou; Zhang, Yan; Chai, Renjie
作者单位1.Zhejiang Univ, MOE Frontier Sci Ctr Brain Res & Brain Machine In, Sch Med, Hangzhou, Peoples R China
2.Zhejiang Univ, Dept Pharmacol, Sch Med, Hangzhou, Peoples R China
3.Southeast Univ, Zhongda Hosp,Jiangsu Prov High Tech Key Lab Biome, Adv Inst Life & Hlth, Sch Life Sci & Technol,Dept Otolaryngol Head & Ne, Nanjing, Peoples R China
4.Zhejiang Univ, Sir Run Run Shaw Hosp, Dept Pathol, Sch Med, Hangzhou, Peoples R China
5.Zhejiang Univ, Liangzhu Lab, Hangzhou, Peoples R China
6.Huazhong Univ Sci & Technol HUST, Coll Life Sci & Technol, Int Res Ctr Sensory Biol & Technol MOST, Key Lab Mol Biophys MOE, Wuhan, Peoples R China
7.Guangzhou Regenerat Med & Hlth Guangdong Lab, Bioland Lab, Guangzhou, Peoples R China
8.Chinese Acad Sci, Shanghai Inst Mat Media, Analyt Res Ctr Organ & Biol Mol, CAS Key Lab Receptor Res,State Key Lab Drug Res, Shanghai, Peoples R China
9.Nantong Univ, Coinnovat Ctr Neuroregenerat, Nantong, Peoples R China
10.Beijing Inst Technol, Aerosp Ctr Hosp, Sch Life Sci, Dept Neurol, Beijing, Peoples R China
推荐引用方式
GB/T 7714		 Ma, Xiangyu,Chen, Li-Nan,Liao, Menghui,et al. Molecular insights into the activation mechanism of GPR156 in maintaining auditory function[J]. NATURE COMMUNICATIONS,2024,15(1):16.
APA Ma, Xiangyu.,Chen, Li-Nan.,Liao, Menghui.,Zhang, Liyan.,Xi, Kun.,...&Chai, Renjie.(2024).Molecular insights into the activation mechanism of GPR156 in maintaining auditory function.NATURE COMMUNICATIONS,15(1),16.
MLA Ma, Xiangyu,et al."Molecular insights into the activation mechanism of GPR156 in maintaining auditory function".NATURE COMMUNICATIONS 15.1(2024):16.

入库方式： OAI收割

来源：上海药物研究所

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