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A Triad of Lys12, Lys41, Arg78 Spatial Domain, a Novel Identified Heparin Binding Site on Tat Protein, Facilitates Tat-Driven Cell Adhesion

文献类型：期刊论文

作者Ai, Jing1; Xin, Xianliang1; Zheng, Mingyue3; Wang, Shuai2; Peng, Shuying4; Li, Jing1; Wang, Limei1; Jiang, Hualiang3; Geng, Meiyu1,2
刊名PLOS ONE
出版日期2008-07-16
卷号3期号:7
ISSN号1932-6203
DOI10.1371/journal.pone.0002662
文献子类Article
英文摘要Tat protein, released by HIV-infected cells, has a battery of important biological effects leading to distinct AIDS-associated pathologies. Cell surface heparan sulfate protoglycans (HSPGs) have been accepted as endogenous Tat receptors, and the Tat basic domain has been identified as the heparin binding site. However, findings that deletion or substitution of the basic domain inhibits but does not completely eliminate Tat-heparin interactions suggest that the basic domain is not the sole Tat heparin binding site. In the current study, an approach integrating computational modeling, mutagenesis, biophysical and cell-based assays was used to elucidate a novel, high affinity heparin-binding site: a Lys12, Lys41, Arg78 (KKR) spatial domain. This domain was also found to facilitate Tat-driven beta 1 integrin activation, producing subsequent SLK cell adhesion in an HSPG-dependent manner, but was not involved in Tat internalization. The identification of this new heparin binding site may foster further insight into the nature of Tat-heparin interactions and subsequent biological functions, facilitating the rational design of new therapeutics against Tat-mediated pathological events.
资助项目National Basic Research Program of China[2003CB716400] ; Natural Science Foundation of China for Distinguished Young Scholars[30725046] ; Natural Science Foundation of Shandong Province[y2004c19]
WOS研究方向Science & Technology - Other Topics
语种英语
WOS记录号WOS:000264057200008
出版者PUBLIC LIBRARY SCIENCE
源URL[http://119.78.100.183/handle/2S10ELR8/272863]  
专题药物发现与设计中心
中科院受体结构与功能重点实验室
新药研究国家重点实验室
药理学第一研究室
通讯作者Ai, Jing
作者单位1.Ocean Univ China, Dept Pharmacol & Glycobiol, Marine Drug & Food Inst, Qingdao, Peoples R China;
2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Div Anti tumor Pharmacol, Shanghai, Peoples R China;
3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Drug Discovery & Design Ctr, Shanghai, Peoples R China;
4.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Anal Chem, Lab Mass Spectrometry, Shanghai, Peoples R China
推荐引用方式
GB/T 7714		 Ai, Jing,Xin, Xianliang,Zheng, Mingyue,et al. A Triad of Lys12, Lys41, Arg78 Spatial Domain, a Novel Identified Heparin Binding Site on Tat Protein, Facilitates Tat-Driven Cell Adhesion[J]. PLOS ONE,2008,3(7).
APA Ai, Jing.,Xin, Xianliang.,Zheng, Mingyue.,Wang, Shuai.,Peng, Shuying.,...&Geng, Meiyu.(2008).A Triad of Lys12, Lys41, Arg78 Spatial Domain, a Novel Identified Heparin Binding Site on Tat Protein, Facilitates Tat-Driven Cell Adhesion.PLOS ONE,3(7).
MLA Ai, Jing,et al."A Triad of Lys12, Lys41, Arg78 Spatial Domain, a Novel Identified Heparin Binding Site on Tat Protein, Facilitates Tat-Driven Cell Adhesion".PLOS ONE 3.7(2008).

入库方式： OAI收割

来源：上海药物研究所

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