alpha-Klotho is a non-enzymatic molecular scaffold for FGF23 hormone signalling

doi:10.1038/nature25451

科研成果详情

题名	alpha-Klotho is a non-enzymatic molecular scaffold for FGF23 hormone signalling
作者	Chen, Gaozhi1,2; Liu, Yang 2; Goetz, Regina 2; Fu, Lili1,2; Jayaraman, Seetharaman 3; Hu, Ming-Chang 4; Moe, Orson W.4; Liang, Guang1; Li, Xiaokun1; Mohammadi, Moosa 2
发表日期	2018-01-25
发表期刊	NATURE 影响因子和分区
语种	英语
原始文献类型	Article
其他关键词	FIBROBLAST-GROWTH-FACTOR ; TRANSCRIPTS ENCODING MEMBRANE ; C-TERMINAL TAIL ; STRUCTURAL BASIS ; BETA-KLOTHO ; FIBROBLAST-GROWTH-FACTOR-1 FGF1 ; METABOLIC-ACTIVITY ; CRYSTAL-STRUCTURE ; RECEPTOR ; HEPARIN
摘要	The ageing suppressor alpha-klotho binds to the fibroblast growth factor receptor (FGFR). This commits FGFR to respond to FGF23, a key hormone in the regulation of mineral ion and vitamin D homeostasis. The role and mechanism of this co-receptor are unknown. Here we present the atomic structure of a 1:1:1 ternary complex that consists of the shed extracellular domain of alpha-klotho, the FGFR1c ligand-binding domain, and FGF23. In this complex, alpha-klotho simultaneously tethers FGFR1c by its D3 domain and FGF23 by its C-terminal tail, thus implementing FGF23-FGFR1c proximity and conferring stability. Dimerization of the stabilized ternary complexes and receptor activation remain dependent on the binding of heparan sulfate, a mandatory cofactor of paracrine FGF signalling. The structure of alpha-klotho is incompatible with its purported glycosidase activity. Thus, shed alpha-klotho functions as an on-demand non-enzymatic scaffold protein that promotes FGF23 signalling.
资助项目	NIH grantUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01 DE13686]; National Key R&D Program of China [2017YFA0506000]; NIH NIGMSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of General Medical Sciences (NIGMS); [R01 DK092461]; [P30 DK079328]; [R01 DK091392]; NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Dental & Craniofacial Research (NIDCR) [R01DE013686] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) [P30DK079328, R01DK091392, R01DK092461] Funding Source: NIH RePORTER
出版者	NATURE PUBLISHING GROUP
出版地	LONDON
ISSN	0028-0836
EISSN	1476-4687
卷号	553 期号:7689 页码:461-+
DOI	10.1038/nature25451
页数	26
WOS类目	Multidisciplinary Sciences
WOS研究方向	Science & Technology - Other Topics
WOS记录号	WOS:000423971100033
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	29342138
PMC记录号	PMC6007875
SCOPUSEID	2-s2.0-85041051833
ESI高被引论文	2020-01 ; 2020-03 ; 2020-05 ; 2020-09 ; 2020-11 ; 2021-01 ; 2021-03 ; 2021-05 ; 2021-07 ; 2021-09 ; 2021-11 ; 2022-01 ; 2022-03 ; 2022-05 ; 2022-07 ; 2022-09 ; 2022-11 ; 2023-01 ; 2023-03 ; 2023-05 ; 2023-07 ; 2023-09 ; 2023-11 ; 2024-01 ; 2024-03 ; 2024-05 ; 2024-07 ; 2024-09
CNS重要论文	CNS重要论文
自科自定义期刊分类	T1类
通讯作者地址	[Li, Xiaokun]Chemical Biology Research Center,School of Pharmaceutical Sciences,Wenzhou Medical University,Wenzhou, Zhejiang,325035,China
Scopus学科分类	Multidisciplinary
TOP期刊	TOP期刊
引用统计	被引频次：219[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/9726
专题	药学院（分析测试中心）药学院（分析测试中心）_生物有机与药物化学研究中心
通讯作者	Li, Xiaokun
作者单位	1.Chemical Biology Research Center,School of Pharmaceutical Sciences,Wenzhou Medical University,Wenzhou, Zhejiang,325035,China; 2.Department of Biochemistry and Molecular Pharmacology,New York University School of Medicine,New York,10016,United States; 3.New York Structural Biology Center,New York,10027,United States; 4.Departments of Internal Medicine and Physiology,Charles and Jane Pak Center of Mineral Metabolism and Clinical Research,University of Texas Southwestern Medical Center,Dallas,75390,United States
第一作者单位	药学院（分析测试中心）; 生物有机与药物化学研究中心
通讯作者单位	药学院（分析测试中心）; 生物有机与药物化学研究中心
第一作者的第一单位	药学院（分析测试中心）
推荐引用方式 GB/T 7714	Chen, Gaozhi,Liu, Yang,Goetz, Regina,et al. alpha-Klotho is a non-enzymatic molecular scaffold for FGF23 hormone signalling[J]. NATURE,2018,553(7689):461-+.
APA	Chen, Gaozhi., Liu, Yang., Goetz, Regina., Fu, Lili., Jayaraman, Seetharaman., ... & Mohammadi, Moosa. (2018). alpha-Klotho is a non-enzymatic molecular scaffold for FGF23 hormone signalling. NATURE, 553(7689), 461-+.
MLA	Chen, Gaozhi,et al."alpha-Klotho is a non-enzymatic molecular scaffold for FGF23 hormone signalling".NATURE 553.7689(2018):461-+.