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| Second messenger Ap(4)A polymerizes target protein HINT1 to transduce signals in Fc epsilon RI-activated mast cells | |
| 2019-10-11 | |
| Source Publication | NATURE COMMUNICATIONS
 |
| ISSN | 2041-1723 |
| Volume | 10 |
| Status | 已发表 |
| DOI | 10.1038/s41467-019-12710-8 |
| Abstract | Signal 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 By | SCI ; SCIE |
| Language | 英语 |
| Funding Project | Hebrew-University-National Research Foundation of Singapore[HUJ-CREATE R182-005-172-281] |
| WOS Research Area | Science & Technology - Other Topics |
| WOS Subject | Multidisciplinary Sciences |
| WOS ID | WOS:000489706400016 |
| Publisher | NATURE PUBLISHING GROUP |
| WOS Keyword | TRANSFER-RNA SYNTHETASE ; TRANSCRIPTIONAL ACTIVITY ; DIADENOSINE 5',5'''-P1,P4-TETRAPHOSPHATE ; AXONAL NEUROPATHY ; TUMOR-SUPPRESSOR ; DI-AMP ; MITF ; MUTATIONS ; SUBSTRATE ; PATHWAY |
| Original Document Type | Article |
| Citation statistics | |
| Document Type | 期刊论文 |
| Identifier | https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/80420 |
| Collection | iHuman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 Author | Razin, Ehud; Wang, Jing |
| Affiliation | 1.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). |
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