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Structural insights into the activation of somatostatin receptor 2 by cyclic SST analogues

文献类型：期刊论文

作者Bo, Qing2,3; Yang, Fan2,3; Li, Yingge2,3; Meng, Xianyu2,3; Zhang, Huanhuan2,3; Zhou, Yingxin2,3; Ling, Shenglong2,3; Sun, Demeng2,3; Lv, Pei2,3; Liu, Lei1
刊名CELL DISCOVERY
出版日期2022-05-20
卷号8
DOI10.1038/s41421-022-00405-2
通讯作者Liu, Lei(lliu@mail.tsinghua.edu.cn) ; Shi, Pan(shipan@ustc.edu.cn) ; Tian, Changlin(cltian@ustc.edu.cn)
英文摘要The endogenous cyclic tetradecapeptide SST14 was reported to stimulate all five somatostatin receptors (SSTR1-5) for hormone release, neurotransmission, cell growth arrest and cancer suppression. Two SST14-derived short cyclic SST analogues (lanreotide or octreotide) with improved stability and longer lifetime were developed as drugs to preferentially activate SSTR2 and treat acromegalia and neuroendocrine tumors. Here, cryo-EM structures of the human SSTR2-Gi complex bound with SST14, octreotide or lanreotide were determined at resolutions of 2.85 angstrom, 2.97 angstrom, and 2.87 angstrom, respectively. Structural and functional analysis revealed that interactions between beta-turn residues in SST analogues and transmembrane SSTR2 residues in the ligand-binding pocket are crucial for receptor binding and functional stimulation of the two SST14-derived cyclic octapeptides. Additionally, Q102(2.63), N276(6.55), and F294(7.35) could be responsible for the selectivity of lanreotide or octreotide for SSTR2 over SSTR1 or SSTR4. These results provide valuable insights into further rational development of SST analogue drugs targeting SSTR2.
WOS关键词NEUROENDOCRINE TUMORS ; IN-VITRO ; OCTAPEPTIDE ANALOG ; CRYO-EM ; OCTREOTIDE ; EXPRESSION ; GROWTH ; VIVO ; SELECTIVITY ; INHIBITION
资助项目National Natural Science Foundation of China[21825703] ; National Natural Science Foundation of China[31971152] ; National Natural Science Foundation of China[22137005] ; National Key R&D Program of China[2016YFA0400903] ; National Key R&D Program of China[2017YFA0505400] ; Strategic Priority Research Program of Chinese Academy of Sciences[XDB37000000] ; Anhui Provincial Natural Science Foundation[2108085J16] ; Collaborative Innovation Program of Hefei Science Center, Chinese Academy of Sciences[2021HSC-CIP011] ; China National Postdoctoral Program for Innovative Talents[BH2340000159]
WOS研究方向Cell Biology
语种英语
WOS记录号WOS:000798186300001
出版者SPRINGERNATURE
资助机构National Natural Science Foundation of China ; National Key R&D Program of China ; Strategic Priority Research Program of Chinese Academy of Sciences ; Anhui Provincial Natural Science Foundation ; Collaborative Innovation Program of Hefei Science Center, Chinese Academy of Sciences ; China National Postdoctoral Program for Innovative Talents
源URL[http://ir.hfcas.ac.cn:8080/handle/334002/130965]  
专题中国科学院合肥物质科学研究院
通讯作者Liu, Lei; Shi, Pan; Tian, Changlin
作者单位1.Tsinghua Univ, Tsinghua Peking Joint Ctr Life Sci, Minist Educ, Key Lab Bioorgan Phosphorus Chem & Chem Biol, Beijing, Peoples R China
2.Univ Sci & Technol China, Dept Chem, Hefei, Anhui, Peoples R China
3.Univ Sci & Technol China, Affiliated Hosp USTC 1, Anhui Engn Lab Peptide Drug,Anhui Lab Adv Photon, Sch Life Sci,Div Life Sci & Med,Joint Ctr Biol An, Hefei, Anhui, Peoples R China
4.Chinese Acad Sci, High Magnet Field Lab, Hefei, Anhui, Peoples R China
推荐引用方式
GB/T 7714		 Bo, Qing,Yang, Fan,Li, Yingge,et al. Structural insights into the activation of somatostatin receptor 2 by cyclic SST analogues[J]. CELL DISCOVERY,2022,8.
APA Bo, Qing.,Yang, Fan.,Li, Yingge.,Meng, Xianyu.,Zhang, Huanhuan.,...&Tian, Changlin.(2022).Structural insights into the activation of somatostatin receptor 2 by cyclic SST analogues.CELL DISCOVERY,8.
MLA Bo, Qing,et al."Structural insights into the activation of somatostatin receptor 2 by cyclic SST analogues".CELL DISCOVERY 8(2022).

入库方式： OAI收割

来源：合肥物质科学研究院

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