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Nanobodies as negative allosteric modulators for human calcium sensing receptor

文献类型：期刊论文

作者Cui, Qianqian5,6; Wang, Lu5; Wang, Haonan5; Chen, Xiaochen5; Han, Li5; Geng, Tengjie5; Kou, Yongjun5; Zhang, Wenqing5; Dai, Mei5; Qiao, Huarui5
刊名BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
出版日期2024-02-05
卷号695页码:9
ISSN号0006-291X
关键词G-protein-coupled receptor Extracellular calcium sensing receptor Nanobody Cryo-electron microscope Systemic Ca 2+homoeostasis
DOI10.1016/j.bbrc.2023.149401
通讯作者Xu, Hongxi(daiyuanyuan@cicams.ac.cn) ; Xu, Jiaqiang(xujiaqiang@shu.edu.cn) ; Dai, Yuanyuan(xuhongxi88@gmail.com) ; Geng, Yong(gengyong@simm.ac.cn)
英文摘要Human calcium sensing receptor (CaSR) senses calcium ion concentrations in vivo and is an important class of drug targets. Mutations in the receptor can lead to disorders of calcium homeostasis, including hypercalcemia and hypocalcemia. Here, 127 CaSR-targeted nanobodies were generated from camels, and four nanobodies with inhibitory function were further identified. Among these nanobodies, NB32 can effectively inhibit the mobilization of intracellular calcium ions (Ca2+i ) and suppress the G12/13 and ERK1/2 signaling pathways downstream of CaSR. Moreover, it enhanced the inhibitory effect of the calcilytics as a negative allosteric modulator (NAM). We determined the structure of complex and found NB32 bound to LB2 (Ligand-binding 2) domain of CaSR to prevent the interaction of LB2 domains of two protomers to stabilize the inactive state of CaSR.
WOS关键词AUTOSOMAL-DOMINANT HYPOCALCEMIA ; EXTRACELLULAR CALCIUM ; ACTIVATING MUTATION ; SECONDARY HYPERPARATHYROIDISM ; GENE ; FAMILY ; CELLS ; CA-2+
资助项目National Natural Science Foundation of China[31670743] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12040326] ; Science and Technology Commission of Shanghai Municipality[3918JC141540001] ; Joint Research Fund for Overseas, Hong Kong and Macao Scholars[81628013] ; Natural Science Foundation of Shanghai[16ZR1442900] ; National Science Foundation for Young Scholar projects[118180359901] ; Shanghai Institute of Materia Medica, the Chinese Academy of Sciences[CASIMM0120164013] ; Shanghai Institute of Materia Medica, the Chinese Academy of Sciences[SIMM1606YZZ-06] ; Shanghai Institute of Materia Medica, the Chinese Academy of Sciences[SIMM1601KF-06] ; Shanghai Institute of Materia Medica, the Chinese Academy of Sciences[55201631121116101] ; Shanghai Institute of Materia Medica, the Chinese Academy of Sciences[55201631121108000] ; Shanghai Institute of Materia Medica, the Chinese Academy of Sciences[5112345601] ; Shanghai Institute of Materia Medica, the Chinese Academy of Sciences[2015123]
WOS研究方向Biochemistry & Molecular Biology ; Biophysics
语种英语
出版者ACADEMIC PRESS INC ELSEVIER SCIENCE
WOS记录号WOS:001165713100001
源URL[http://119.78.100.183/handle/2S10ELR8/309922]  
专题中国科学院上海药物研究所
通讯作者Xu, Hongxi; Xu, Jiaqiang; Dai, Yuanyuan; Geng, Yong
作者单位1.Chinese Acad Med Sci, Peking Union Med Coll, Beijing 100021, Peoples R China
2.Chinese Acad Med Sci, Natl Canc Ctr, Dept Pharm, Natl Clin Res Ctr Canc,Canc Hosp, Beijing 100021, Peoples R China
3.Shanghai Univ Tradit Chinese Med, Sch Pharm, Shanghai 201203, Peoples R China
4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
5.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Stake Key Lab Drug Res, Shanghai 201203, Peoples R China
6.Shanghai Univ, Coll Sci, Dept Chem, NEST Lab, Shanghai 200444, Peoples R China
推荐引用方式
GB/T 7714		 Cui, Qianqian,Wang, Lu,Wang, Haonan,et al. Nanobodies as negative allosteric modulators for human calcium sensing receptor[J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,2024,695:9.
APA Cui, Qianqian.,Wang, Lu.,Wang, Haonan.,Chen, Xiaochen.,Han, Li.,...&Geng, Yong.(2024).Nanobodies as negative allosteric modulators for human calcium sensing receptor.BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,695,9.
MLA Cui, Qianqian,et al."Nanobodies as negative allosteric modulators for human calcium sensing receptor".BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 695(2024):9.

入库方式： OAI收割

来源：上海药物研究所

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