Second messenger Ap(4)A polymerizes target protein HINT1 to transduce signals in Fc epsilon RI-activated mast cells
Yu, Jing1; Liu, Zaizhou1; Liang, Yuanyuan1; Luo, Feng2; Zhang, Jie1; Tian, Cuiping3; Motzik, Alex4; Zheng, Mengmeng1; Kang, Jingwu1; Zhong, Guisheng3; Liu, Cong2; Fang, Pengfei1; Guo, Min1,5; Razin, Ehud4,6; Wang, Jing1
2019-10-11
Source PublicationNATURE COMMUNICATIONS
ISSN2041-1723
Volume10
Status已发表
DOI10.1038/s41467-019-12710-8
AbstractSignal transduction systems enable organisms to monitor their external environments and accordingly adjust the cellular processes. In mast cells, the second messenger Ap(4)A binds to the histidine triad nucleotide-binding protein 1 (HINT1), disrupts its interaction with the microphthalmia-associated transcription factor (MITF), and eventually activates the transcription of genes downstream of MITF in response to immunostimulation. How the HINT1 protein recognizes and is regulated by Ap(4)A remain unclear. Here, using eight crystal structures, biochemical experiments, negative stain electron microscopy, and cellular experiments, we report that Ap(4)A specifically polymerizes HINT1 in solution and in activated rat basophilic leukemia cells. The polymerization interface overlaps with the area on HINT1 for MITF interaction, suggesting a possible competitive mechanism to release MITF for transcriptional activation. The mechanism depends precisely on the length of the phosphodiester linkage of Ap(4)A. These results highlight a direct polymerization signaling mechanism by the second messenger.
URL查看原文
Indexed BySCI
Language英语
Funding ProjectHebrew-University-National Research Foundation of Singapore[HUJ-CREATE R182-005-172-281]
WOS Research AreaScience & Technology - Other Topics
WOS SubjectMultidisciplinary Sciences
WOS IDWOS:000489706400016
PublisherNATURE PUBLISHING GROUP
WOS KeywordTRANSFER-RNA SYNTHETASE ; TRANSCRIPTIONAL ACTIVITY ; DIADENOSINE 5',5'''-P1,P4-TETRAPHOSPHATE ; AXONAL NEUROPATHY ; TUMOR-SUPPRESSOR ; DI-AMP ; MITF ; MUTATIONS ; SUBSTRATE ; PATHWAY
Original Document TypeArticle
Citation statistics
Cited Times [WOS]:0   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttps://kms.shanghaitech.edu.cn/handle/2MSLDSTB/80420
CollectioniHuman研究所_公共科研平台_超分辨生物成像平台
iHuman研究所_PI研究组_钟桂生组
Corresponding AuthorRazin, Ehud; Wang, Jing
Affiliation1.Univ Chinese Acad Sci, Chinese Acad Sci, State Key Lab Bioorgan & Nat Prod Chem, Ctr Excellence Mol Synth,Shanghai Inst Organ Chem, 345 Lingling Rd, Shanghai 200032, Peoples R China
2.Chinese Acad Sci, Interdisciplinary Res Ctr Biol & Chem, Shanghai Inst Organ Chem, Shanghai 201210, Peoples R China
3.ShanghaiTech Univ, iHuman Inst, Shanghai 201210, Peoples R China
4.Hebrew Univ Jerusalem, Med Sch, Dept Biochem & Mol Biol, Inst Med Res Israel Canada, IL-91120 Jerusalem, Israel
5.Kangma BioTech Co Ltd, 1131 Cailun Rd, Shanghai 201203, Peoples R China
6.Natl Univ Singapore, NUS HUJ CREATE Cellular & Mol Mech Inflammat Prog, Dept Microbiol & Immunol, Singapore 117597, Singapore
Recommended Citation
GB/T 7714
Yu, Jing,Liu, Zaizhou,Liang, Yuanyuan,et al. Second messenger Ap(4)A polymerizes target protein HINT1 to transduce signals in Fc epsilon RI-activated mast cells[J]. NATURE COMMUNICATIONS,2019,10.
APA Yu, Jing.,Liu, Zaizhou.,Liang, Yuanyuan.,Luo, Feng.,Zhang, Jie.,...&Wang, Jing.(2019).Second messenger Ap(4)A polymerizes target protein HINT1 to transduce signals in Fc epsilon RI-activated mast cells.NATURE COMMUNICATIONS,10.
MLA Yu, Jing,et al."Second messenger Ap(4)A polymerizes target protein HINT1 to transduce signals in Fc epsilon RI-activated mast cells".NATURE COMMUNICATIONS 10(2019).
Files in This Item: Download All
File Name/Size DocType Version Access License
10.1038@s41467-019-1(2466KB)期刊论文未知开放获取UnknownView Download
Related Services
Usage statistics
Scholar Google
Similar articles in Scholar Google
[Yu, Jing]'s Articles
[Liu, Zaizhou]'s Articles
[Liang, Yuanyuan]'s Articles
Baidu academic
Similar articles in Baidu academic
[Yu, Jing]'s Articles
[Liu, Zaizhou]'s Articles
[Liang, Yuanyuan]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[Yu, Jing]'s Articles
[Liu, Zaizhou]'s Articles
[Liang, Yuanyuan]'s Articles
Terms of Use
No data!
Social Bookmark/Share
File name: 10.1038@s41467-019-12710-8.pdf
Format: Adobe PDF
All comments (0)
No comment.
 

Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.