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学科主题: 药学
题名:
Determinants of the membrane orientation of a calcium signaling enzyme CD38
作者: Zhao, Yong Juan1,2; Zhu, Wen Jie1; Wang, Xian Wang3; Zhang, Li-He1,4; Lee, Hon Cheung1
关键词: CD38 ; Cyclic ADP-ribose ; Membrane topology ; ADP-ribosyl cyclase ; Calcium signaling
刊名: BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
发表日期: 2015-09-01
DOI: 10.1016/j.bbamcr.2014.10.028
卷: 1853, 期:9, 页:2095-2103
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemistry & Molecular Biology ; Cell Biology
研究领域[WOS]: Biochemistry & Molecular Biology ; Cell Biology
关键词[WOS]: CYCLIC-ADP-RIBOSE ; ENDOPLASMIC-RETICULUM ; CRYSTAL-STRUCTURE ; CYCLASE ACTIVITY ; PROTEIN ; TOPOLOGY ; CELLS ; ACID ; CA2+ ; PHOSPHORYLATION
英文摘要:

CD38 catalyzes the synthesis of two structurally distinct messengers for Ca2+-mobilization, cyclic ADP-ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate (NAADP), from cytosolic substrates, NAD and NADP, respectively. CD38 is generally thought of as a type II membrane protein with its catalytic site facing outside. We recently showed that CD38 exists, instead, in two opposite membrane orientations. The determinant for the membrane topology is unknown. Here, specific antibodies against type III CD38 were designed and produced. We show that mutating the positively charged residues in the N-terminal tail of CD38 converted its orientation to type III, with the catalytic domain facing the cytosol and it was fully active in producing intracellular cADPR. Changing the serine residues to aspartate, which is functionally equivalent to phosphotylation, had a similar effect. The mutated CD38 was expressed intracellularly and was un-glycosylated. The membrane topology could also be modulated by changing the highly conserved di-cysteine. The results indicate that the net charge of the N-terminal segment is important in determining the membrane topology of CD38 and that the type III orientation can be a functional form of CD38 for Ca2+-signaling. This article is part of a Special Issue entitled: 13th European Symposium on Calcium. (C) 2014 Elsevier B.V. All rights reserved.

语种: 英语
所属项目编号: JCYJ20130331144947526 ; 31301156 ; 31470815 ; 91413114 ; 770610 ; 770111 ; 769912
项目资助者: Shenzhen Government ; National Science Foundation of China ; Research Grants Council of Hong Kong
WOS记录号: WOS:000359960400021
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/50634
Appears in Collections:北京大学药学院_期刊论文

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作者单位: 1.Peking Univ, Shenzhen Grad Sch, Sch Chem Biol & Biotechnol, Shenzhen, Peoples R China
2.Univ Hong Kong, Dept Physiol, Pokfulam, Hong Kong, Peoples R China
3.Yangtze Univ, Sch Med, Funct Lab, Jingzhou, Hubei, Peoples R China
4.Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100871, Peoples R China

Recommended Citation:
Zhao, Yong Juan,Zhu, Wen Jie,Wang, Xian Wang,et al. Determinants of the membrane orientation of a calcium signaling enzyme CD38[J]. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH,2015,1853(9):2095-2103.
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