Second messenger Ap(4)A polymerizes target protein HINT1 to transduce signals in Fc epsilon RI-activated mast cells

doi:10.1038/s41467-019-12710-8

	Second messenger Ap(4)A polymerizes target protein HINT1 to transduce signals in Fc epsilon RI-activated mast cells
	Yu, Jing 1; Liu, Zaizhou 1; Liang, Yuanyuan 1; Luo, Feng 2; Zhang, Jie 1; Tian, Cuiping3 ; Motzik, Alex 4; Zheng, Mengmeng 1; Kang, Jingwu 1; Zhong, Guisheng3 ; Liu, Cong 2; Fang, Pengfei 1; Guo, Min 1,5; Razin, Ehud 4,6; Wang, Jing 1
	2019-10-11
发表期刊	NATURE COMMUNICATIONS
ISSN	2041-1723
卷号	10
发表状态	已发表
DOI	10.1038/s41467-019-12710-8
摘要	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.
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收录类别	SCI ; SCIE
语种	英语
资助项目	Hebrew-University-National Research Foundation of Singapore[HUJ-CREATE R182-005-172-281]
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:000489706400016
出版者	NATURE PUBLISHING GROUP
WOS关键词	TRANSFER-RNA SYNTHETASE ; TRANSCRIPTIONAL ACTIVITY ; DIADENOSINE 5',5'''-P1,P4-TETRAPHOSPHATE ; AXONAL NEUROPATHY ; TUMOR-SUPPRESSOR ; DI-AMP ; MITF ; MUTATIONS ; SUBSTRATE ; PATHWAY
原始文献类型	Article
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/80420
专题	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
通讯作者	Razin, Ehud; Wang, Jing
作者单位	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
推荐引用方式 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).