题名 | alpha-Klotho is a non-enzymatic molecular scaffold for FGF23 hormone signalling |
作者 | |
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 |
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 |
发表日期 | 2018-01-25 |
URL | 查看原文 |
Pubmed记录号 | 29342138 |
PMC记录号 | PMC6007875 |
Scopus记录号 | 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 |
CNS重要论文 | CNS重要论文 |
自科自定义期刊分类 | T1类 |
引用统计 | |
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) |
通讯作者 | Li, Xiaokun; Mohammadi, Moosa |
作者单位 | 1.Wenzhou Med Univ, Sch Pharmaceut Sci, Chem Biol Res Ctr, Wenzhou 325035, Zhejiang, Peoples R China; 2.NYU, Sch Med, Dept Biochem & Mol Pharmacol, New York, NY 10016 USA; 3.New York Struct Biol Ctr, New York, NY 10027 USA; 4.Univ Texas Southwestern Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA; 5.Univ Texas Southwestern Med Ctr Dallas, Dept Physiol, Dallas, TX 75390 USA; 6.Univ Texas Southwestern Med Ctr Dallas, Charles & Jane Pak Ctr Mineral Metab & Clin Res, Dallas, TX 75390 USA |
第一作者单位 | 药学院(分析测试中心) |
通讯作者单位 | 药学院(分析测试中心) |
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-+. |
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