Elucidation of Distinct Modular Assemblies of Smoothened Receptor by Bitopic Ligand Measurement

doi:10.1021/acs.jmedchem.1c01220

	Elucidation of Distinct Modular Assemblies of Smoothened Receptor by Bitopic Ligand Measurement
	Zhao, Fei1 ; Wu, Yiran1 ; Zhou, Fang1 ; Xue, Dongxiang1 ; Zhao, Simeng1 ; Lu, Wanglong 2; Liu, Xiaoyan1 ; Hu, Tao1,3 ; Qiu, Yanli1,3 ; Li, Rongyan 1,3; Gu, Tangjie4 ; Xu, Yueming1 ; Xu, Fei1,3 ; Zhong, Guisheng1,3 ; Jiang, Zhongxing 2; Zhao, Suwen1,3 ; Tao, Houchao1
	2021-09-23
发表期刊	JOURNAL OF MEDICINAL CHEMISTRY (IF:6.8[JCR-2023],7.1[5-Year])
ISSN	0022-2623
EISSN	1520-4804
卷号	64 期号:18 页码:13830-13840
DOI	10.1021/acs.jmedchem.1c01220
摘要	Class F G protein-coupled receptors are characterized by a large extracellular domain (ECD) in addition to the common transmembrane domain (TMD) with seven alpha-helixes. For smoothened receptor (SMO), structural studies revealed dissected ECD and TMD, and their integrated assemblies. However, distinct assemblies were reported under different circumstances. Using an unbiased approach based on four series of cross-conjugated bitopic ligands, we explore the relationship between the active status and receptor assembly. Different activity dependency on the linker length for these bitopic ligands corroborates the various occurrences of SMO assembly. These results reveal a rigid near assembly for active SMO, which is in contrast to previous results. Conversely, inactive SMO adopts a free ECD, which would be remotely captured at far assembly by cholesterol. Altogether, we propose a mechanism of cholesterol flow-caused SMO activation involving an erection of ECD from far to near assembly.
收录类别	SCIE ; IC
语种	英语
WOS研究方向	Pharmacology & Pharmacy
WOS类目	Chemistry, Medicinal
WOS记录号	WOS:000701513400042
出版者	AMER CHEMICAL SOC
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/128323
专题	iHuman研究所_PI研究组_陶厚朝组 iHuman研究所_公共科研平台_IT平台 iHuman研究所_公共科研平台_动物细胞培养和蛋白纯化平台 iHuman研究所_PI研究组_徐菲组 iHuman研究所_PI研究组_赵素文组 iHuman研究所_PI研究组_钟桂生组生命科学与技术学院_硕士生物质科学与技术学院_硕士生生命科学与技术学院_博士生
通讯作者	Zhao, Suwen; Tao, Houchao
作者单位	1.ShanghaiTech Univ, iHuman Inst, Shanghai 201210, Peoples R China; 2.Wuhan Univ, Sch Pharmaceut Sci, Wuhan 430071, Hubei, Peoples R China; 3.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China; 4.ShanghaiTech Univ, Sch Phys Sci & Technol, Shanghai 201210, Peoples R China
第一作者单位	iHuman研究所
通讯作者单位	iHuman研究所; 生命科学与技术学院
第一作者的第一单位	iHuman研究所
推荐引用方式 GB/T 7714	Zhao, Fei,Wu, Yiran,Zhou, Fang,et al. Elucidation of Distinct Modular Assemblies of Smoothened Receptor by Bitopic Ligand Measurement[J]. JOURNAL OF MEDICINAL CHEMISTRY,2021,64(18):13830-13840.
APA	Zhao, Fei.,Wu, Yiran.,Zhou, Fang.,Xue, Dongxiang.,Zhao, Simeng.,...&Tao, Houchao.(2021).Elucidation of Distinct Modular Assemblies of Smoothened Receptor by Bitopic Ligand Measurement.JOURNAL OF MEDICINAL CHEMISTRY,64(18),13830-13840.
MLA	Zhao, Fei,et al."Elucidation of Distinct Modular Assemblies of Smoothened Receptor by Bitopic Ligand Measurement".JOURNAL OF MEDICINAL CHEMISTRY 64.18(2021):13830-13840.