A switch-on mechanism to activate maize ribosome-inactivating protein for targeting HIV-infected cells

	A switch-on mechanism to activate maize ribosome-inactivating protein for targeting HIV-infected cells
	Law SKY 1; Wang RR 2; Mak ANS 1; Wong KB 1; Zheng YT2; Shaw PC1; zhengyt@mail.kiz.ac.cn ; pcshaw@cuhk.edu.hk
	2010
发表期刊	NUCLEIC ACIDS RESEARCH
卷号	38 期号:19 页码:6803–6812
合作性质	其它
摘要	Maize ribosome-inactivating protein (RIP) is a plant toxin that inactivates eukaryotic ribosomes by depurinating a specific adenine residue at the alpha-sarcin/ricin loop of 28S rRNA. Maize RIP is first produced as a proenzyme with a 25-amino acid internal inactivation region on the protein surface. During germination, proteolytic removal of this internal inactivation region generates the active heterodimeric maize RIP with full N-glycosidase activity. This naturally occurring switch-on mechanism provides an opportunity for targeting the cytotoxin to pathogen-infected cells. Here, we report the addition of HIV-1 protease recognition sequences to the internal inactivation region and the activation of the maize RIP variants by HIV-1 protease in vitro and in HIV-infected cells. Among the variants generated, two were cleaved efficiently by HIV-1 protease. The HIV-1 protease-activated variants showed enhanced N-glycosidase activity in vivo as compared to their un-activated counterparts. They also possessed potent inhibitory effect on p24 antigen production in human T cells infected by two HIV-1 strains. This switch-on strategy for activating the enzymatic activity of maize RIP in target cells provides a platform for combating pathogens with a specific protease.
资助者	For work in Hong Kong: Research Grants Council of Hong Kong SAR (CUHK4606/06M); University Grants Council of Hong Kong SAR One-Off Special Equipment Grant (SEG CUHK08). For work in Kunming: 973 Program (2009CB522306); CAS (KSCX1-YW-R-24); Key Scientific and Technological projects of China (2009ZX09501-029, 2008ZX10001-015, 2008ZX10005- 005). Funding for open access charge: Department of Biochemistry; The Chinese University of Hong Kong. ; For work in Hong Kong: Research Grants Council of Hong Kong SAR (CUHK4606/06M); University Grants Council of Hong Kong SAR One-Off Special Equipment Grant (SEG CUHK08). For work in Kunming: 973 Program (2009CB522306); CAS (KSCX1-YW-R-24); Key Scientific and Technological projects of China (2009ZX09501-029, 2008ZX10001-015, 2008ZX10005- 005). Funding for open access charge: Department of Biochemistry; The Chinese University of Hong Kong. ; For work in Hong Kong: Research Grants Council of Hong Kong SAR (CUHK4606/06M); University Grants Council of Hong Kong SAR One-Off Special Equipment Grant (SEG CUHK08). For work in Kunming: 973 Program (2009CB522306); CAS (KSCX1-YW-R-24); Key Scientific and Technological projects of China (2009ZX09501-029, 2008ZX10001-015, 2008ZX10005- 005). Funding for open access charge: Department of Biochemistry; The Chinese University of Hong Kong. ; For work in Hong Kong: Research Grants Council of Hong Kong SAR (CUHK4606/06M); University Grants Council of Hong Kong SAR One-Off Special Equipment Grant (SEG CUHK08). For work in Kunming: 973 Program (2009CB522306); CAS (KSCX1-YW-R-24); Key Scientific and Technological projects of China (2009ZX09501-029, 2008ZX10001-015, 2008ZX10005- 005). Funding for open access charge: Department of Biochemistry; The Chinese University of Hong Kong.
收录类别	SCI
语种	英语
资助者	For work in Hong Kong: Research Grants Council of Hong Kong SAR (CUHK4606/06M); University Grants Council of Hong Kong SAR One-Off Special Equipment Grant (SEG CUHK08). For work in Kunming: 973 Program (2009CB522306); CAS (KSCX1-YW-R-24); Key Scientific and Technological projects of China (2009ZX09501-029, 2008ZX10001-015, 2008ZX10005- 005). Funding for open access charge: Department of Biochemistry; The Chinese University of Hong Kong. ; For work in Hong Kong: Research Grants Council of Hong Kong SAR (CUHK4606/06M); University Grants Council of Hong Kong SAR One-Off Special Equipment Grant (SEG CUHK08). For work in Kunming: 973 Program (2009CB522306); CAS (KSCX1-YW-R-24); Key Scientific and Technological projects of China (2009ZX09501-029, 2008ZX10001-015, 2008ZX10005- 005). Funding for open access charge: Department of Biochemistry; The Chinese University of Hong Kong. ; For work in Hong Kong: Research Grants Council of Hong Kong SAR (CUHK4606/06M); University Grants Council of Hong Kong SAR One-Off Special Equipment Grant (SEG CUHK08). For work in Kunming: 973 Program (2009CB522306); CAS (KSCX1-YW-R-24); Key Scientific and Technological projects of China (2009ZX09501-029, 2008ZX10001-015, 2008ZX10005- 005). Funding for open access charge: Department of Biochemistry; The Chinese University of Hong Kong. ; For work in Hong Kong: Research Grants Council of Hong Kong SAR (CUHK4606/06M); University Grants Council of Hong Kong SAR One-Off Special Equipment Grant (SEG CUHK08). For work in Kunming: 973 Program (2009CB522306); CAS (KSCX1-YW-R-24); Key Scientific and Technological projects of China (2009ZX09501-029, 2008ZX10001-015, 2008ZX10005- 005). Funding for open access charge: Department of Biochemistry; The Chinese University of Hong Kong.
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/6428
专题	科研部门_分子免疫药理学（郑永唐）科研部门_动物模型与人类重大疾病机理重点实验室
通讯作者	zhengyt@mail.kiz.ac.cn; pcshaw@cuhk.edu.hk
作者单位	1.Department of Biochemistry and Centre for Protein Science and Crystallography, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong 2.Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China
推荐引用方式 GB/T 7714	Law SKY,Wang RR,Mak ANS,et al. A switch-on mechanism to activate maize ribosome-inactivating protein for targeting HIV-infected cells[J]. NUCLEIC ACIDS RESEARCH,2010,38(19):6803–6812.
APA	Law SKY.,Wang RR.,Mak ANS.,Wong KB.,Zheng YT*.,...&pcshaw@cuhk.edu.hk.(2010).A switch-on mechanism to activate maize ribosome-inactivating protein for targeting HIV-infected cells.NUCLEIC ACIDS RESEARCH,38(19),6803–6812.
MLA	Law SKY,et al."A switch-on mechanism to activate maize ribosome-inactivating protein for targeting HIV-infected cells".NUCLEIC ACIDS RESEARCH 38.19(2010):6803–6812.

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