Structural basis of Ornithine Decarboxylase inactivation and accelerated degradation by polyamine sensor Antizyme1

doi:10.1038/srep14738

KMS > 免疫化学研究所 > 特聘教授组 > Sachdev S.Sidhu组

	Structural basis of Ornithine Decarboxylase inactivation and accelerated degradation by polyamine sensor Antizyme1
	Wu, Donghui1,5 ; Kaan, Hung Yi Kristal 1; Zheng, Xiaoxia 2,3; Tang, Xuhua 1; He, Yang 2,3; Tan, Qianmin Vanessa 1; Zhang, Neng 1; Song, Haiwei 1,2,3,4
	2015-10-07
发表期刊	SCIENTIFIC REPORTS (IF:3.8[JCR-2023],4.3[5-Year])
ISSN	2045-2322
卷号	5
发表状态	已发表
DOI	10.1038/srep14738
摘要	Ornithine decarboxylase (ODC) catalyzes the first and rate-limiting step of polyamine biosynthesis in humans. Polyamines are essential for cell proliferation and are implicated in cellular processes, ranging from DNA replication to apoptosis. Excessive accumulation of polyamines has a cytotoxic effect on cells and elevated level of ODC activity is associated with cancer development. To maintain normal cellular proliferation, regulation of polyamine synthesis is imposed by Antizyme1 (AZ1). The expression of AZ1 is induced by a ribosomal frameshifting mechanism in response to increased intracellular polyamines. AZ1 regulates polyamine homeostasis by inactivating ODC activity and enhancing its degradation. Here, we report the structure of human ODC in complex with N-terminally truncated AZ1 (cAZ1). The structure shows cAZ1 binding to ODC, which occludes the binding of a second molecule of ODC to form the active homodimer. Consequently, the substrate binding site is disrupted and ODC is inactivated. Structural comparison shows that the binding of cAZ1 to ODC causes a global conformational change of ODC and renders its C-terminal region flexible, therefore exposing this region for degradation by the 26S proteasome. Our structure provides the molecular basis for the inactivation of ODC by AZ1 and sheds light on how AZ1 promotes its degradation.
收录类别	SCI
语种	英语
资助项目	Natural Science Foundation of China[31470723] ; Natural Science Foundation of China[81572698]
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:000362332700001
出版者	NATURE PUBLISHING GROUP
WOS关键词	X-RAY-STRUCTURE ; TRYPANOSOMA-BRUCEI ; ANGSTROM RESOLUTION ; NEOPLASTIC GROWTH ; PROTEIN ; CELLS ; TARGET ; DIFLUOROMETHYLORNITHINE ; CHEMOPREVENTION ; RECOGNITION
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/2112
专题	免疫化学研究所_特聘教授组_抗体工程学实验室
通讯作者	Song, Haiwei
作者单位	1.Inst Mol & Cell Biol, Singapore 138673, Singapore 2.Zhejiang Univ, Life Sci Inst, Hangzhou 310058, Zhejiang, Peoples R China 3.Zhejiang Univ, Innovat Ctr Cell Signaling Network, Hangzhou 310058, Zhejiang, Peoples R China 4.Natl Univ Singapore, Dept Biochem, Singapore 117543, Singapore 5.ShanghaiTech Univ, Shanghai Inst Adv Immunochem Studies, Shanghai 201210, Peoples R China
第一作者单位	免疫化学研究所
推荐引用方式 GB/T 7714	Wu, Donghui,Kaan, Hung Yi Kristal,Zheng, Xiaoxia,et al. Structural basis of Ornithine Decarboxylase inactivation and accelerated degradation by polyamine sensor Antizyme1[J]. SCIENTIFIC REPORTS,2015,5.
APA	Wu, Donghui.,Kaan, Hung Yi Kristal.,Zheng, Xiaoxia.,Tang, Xuhua.,He, Yang.,...&Song, Haiwei.(2015).Structural basis of Ornithine Decarboxylase inactivation and accelerated degradation by polyamine sensor Antizyme1.SCIENTIFIC REPORTS,5.
MLA	Wu, Donghui,et al."Structural basis of Ornithine Decarboxylase inactivation and accelerated degradation by polyamine sensor Antizyme1".SCIENTIFIC REPORTS 5(2015).