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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
Structural insights into ligand recognition and selectivity of somatostatin receptors

文献类型：期刊论文

作者Zhao, Wenli9,10,11; Han, Shuo8,10,11; Qiu, Na9,10,11; Feng, Wenbo7; Lu, Mengjie9,10,11; Zhang, Wenru6; Wang, Mu5,10,11; Zhou, Qingtong7; Chen, Shutian9,10,11; Xu, Wei9,10,11
刊名CELL RESEARCH
出版日期2022-06-23
页码12
ISSN号1001-0602
DOI10.1038/s41422-022-00679-x
通讯作者Yang, Dehua(dhyang@simm.ac.cn) ; Wang, Ming-Wei(mwwang@simm.ac.cn) ; Wu, Beili(beiliwu@simm.ac.cn) ; Zhao, Qiang(zhaoq@simm.ac.cn)
英文摘要Somatostatin receptors (SSTRs) play versatile roles in inhibiting the secretion of multiple hormones such as growth hormone and thyroid-stimulating hormone, and thus are considered as targets for treating multiple tumors. Despite great progress made in therapeutic development against this diverse receptor family, drugs that target SSTRs still show limited efficacy with preferential binding affinity and conspicuous side-effects. Here, we report five structures of SSTR2 and SSTR4 in different states, including two crystal structures of SSTR2 in complex with a selective peptide antagonist and a non-peptide agonist, respectively, a cryo-electron microscopy (cryo-EM) structure of G(i1)-bound SSTR2 in the presence of the endogenous ligand SST-14, as well as two cryo-EM structures of G(i1)-bound SSTR4 in complex with SST-14 and a small-molecule agonist J-2156, respectively. By comparison of the SSTR structures in different states, molecular mechanisms of agonism and antagonism were illustrated. Together with computational and functional analyses, the key determinants responsible for ligand recognition and selectivity of different SSTR subtypes and multiform binding modes of peptide and non-peptide ligands were identified. Insights gained in this study will help uncover ligand selectivity of various SSTRs and accelerate the development of new molecules with better efficacy by targeting SSTRs.
WOS关键词3-DIMENSIONAL CONSENSUS STRUCTURE ; IDENTIFICATION ; PEPTIDE ; ANTAGONISTS ; SECRETION ; AGONISTS ; ANALOGS
资助项目National Key R&D Program of China[2018YFA0507000] ; CAS Strategic Priority Research Program[XDB37030100] ; Shanghai Pilot Program for Basic Research-Chinese Academy of Sciences, Shanghai Branch[JCYJ-SHFY-2021-008] ; National Natural Science Foundation of China[32161133011] ; National Natural Science Foundation of China[31825010] ; National Natural Science Foundation of China[82121005] ; National Natural Science Foundation of China[81872915] ; National Natural Science Foundation of China[82073904] ; National Natural Science Foundation of China[81773792] ; National Natural Science Foundation of China[81973373] ; National Natural Science Foundation of China[21704064]
WOS研究方向Cell Biology
语种英语
出版者SPRINGERNATURE
WOS记录号WOS:000814922200001
源URL[http://119.78.100.183/handle/2S10ELR8/301626]  
专题新药研究国家重点实验室
通讯作者Yang, Dehua; Wang, Ming-Wei; Wu, Beili; Zhao, Qiang
作者单位1.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan, Guangdong, Peoples R China
2.Regor Therapeut, Shanghai, Peoples R China
3.Amgen Asia R&D Ctr, Shanghai, Peoples R China
4.Chinese Acad Sci, Natl Ctr Drug Screening, Shanghai Inst Mat Med, Shanghai, Peoples R China
5.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China
6.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing, Jiangsu, Peoples R China
7.Fudan Univ, Sch Basic Med Sci, Dept Pharmacol, Shanghai, Peoples R China
8.UCAS, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou, Zhejiang, Peoples R China
9.Univ Chinese Acad Sci, Beijing, Peoples R China
10.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai, Peoples R China
推荐引用方式
GB/T 7714		 Zhao, Wenli,Han, Shuo,Qiu, Na,et al. Structural insights into ligand recognition and selectivity of somatostatin receptors[J]. CELL RESEARCH,2022:12.
APA Zhao, Wenli.,Han, Shuo.,Qiu, Na.,Feng, Wenbo.,Lu, Mengjie.,...&Zhao, Qiang.(2022).Structural insights into ligand recognition and selectivity of somatostatin receptors.CELL RESEARCH,12.
MLA Zhao, Wenli,et al."Structural insights into ligand recognition and selectivity of somatostatin receptors".CELL RESEARCH (2022):12.

入库方式： OAI收割

来源：上海药物研究所

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