利用多肽片段相互作用策略研究动态结构变化蛋白质的分子作用全貌
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- 英文论文题名：Study dynamic protein interactions using a fragment-based strategy
- 论文作者：郑保华 ; 王昆 ; 张贵英 ; 姜喜凤 ; 刘克良 ; 程远国 ; 蔡利锋
- 英文论文作者：Baohua Zheng ; K.Wang ; G.Y.Zhang ; X.F.Jiang ; K.L.Liu ; Y.G.Cheng ; L.F.Cai ; Beijing Inst. Pharmacol. and Toxicol. ; Beijing Inst. Microbiol. Epidemiol.
- 年：2016
- 作者机构：北京毒物药物研究所;北京微生物流行病研究所;
- 论文关键词：卷曲螺旋蛋白相互作用 ; 病毒-细胞膜融合 ; 包膜糖蛋白 ; HIV-1 ; gp41
- 会议召开时间：2016-07-01
- 会议录名称：中国化学会第30届学术年会摘要集-第二十八分会：化学生物学
- 语种：中文
- 分类号：R392
- 学会代码：ZGHY
- 会议名称：中国化学会第30届学术年会-第二十八分会 ; 化学生物学
- 会议地点：中国辽宁大连
- 主办单位：中国化学会
- 学会名称：中国化学会
- 页数：1
- 文件大小：160k
- 原文格式：D
- 会议级别：全国
摘要
包膜糖蛋白Env介导的病毒-细胞膜融合是包膜病毒感染宿主细胞的重要途径,感染时,在多种细胞受体或辅助受体作用下,Env经系列严格时空控制的结构变化,促进病毒-细胞膜融合,完成感染~([1])。明确Env结构变化全貌是药物设计、疫苗研发和开发新型病毒检测技术的关键。以HIV-1感染为例,其gp41糖蛋白依次经历高能态结构、前发卡伸展结构、六螺旋束结构系列高度协同的结构变化,保证病毒-细胞膜顺利融合。虽然多种病毒的融合核心结构已解出,但对其动态结构变化的全貌还缺乏了解,制约着高效抗病毒药物和疫苗开发。根据Env跨膜亚基间卷曲螺旋蛋白相互作用本质,我们发展了一种通过研究多肽片段间相互作用探测动态结构变化蛋白质分子作用全貌的策略。将此策略用于HIV-1感染机制研究,我们发现了系列新型高活性多肽和对应靶点,构建出系列稳定活性中间体,加深了对HIV-1感染过程中gp41动态结构变化全貌的理解。该研究有望成为模型用于多种重要相关病毒感染机制的研究。
Enveloped viruses infect host cells through an envelope glycoprotein(Env) mediated virus-cell membrane fusion.In virus infection,Env leads a series strictly temporal controlled structural change to facilited virus-cell membrane fusion,and understanding these details is critical in anti-viral therapeutics.In HIV-1 infection,the glycoprotein gp41 undergoes high-energy conformation,pre-hairpin structure and six-helical bundle conformation,to guide proper viral-cell membrane fusion.Crystal structure of Env fusion core from various viruses have been reported,however lack of the details of dynamic structural changes of the Env hinder high-efficient therapeutic development.Based on coiled-coil interaction nature of HIV-1 gp41,we developed a strategy to probe dynamic protein-protein interactions through study the interaction of peptide fragments that composed the protein.Applying the strategy,we provided a global picture of intra-molecular interactions of gp41 in HIV-1 infection,and identified series novel high-potent peptide HIV-1 fusion inhibitor and stable structural intermediates.Our work provided a model to study infections of other viruses using a similar mechanism.
Enveloped viruses infect host cells through an envelope glycoprotein(Env) mediated virus-cell membrane fusion.In virus infection,Env leads a series strictly temporal controlled structural change to facilited virus-cell membrane fusion,and understanding these details is critical in anti-viral therapeutics.In HIV-1 infection,the glycoprotein gp41 undergoes high-energy conformation,pre-hairpin structure and six-helical bundle conformation,to guide proper viral-cell membrane fusion.Crystal structure of Env fusion core from various viruses have been reported,however lack of the details of dynamic structural changes of the Env hinder high-efficient therapeutic development.Based on coiled-coil interaction nature of HIV-1 gp41,we developed a strategy to probe dynamic protein-protein interactions through study the interaction of peptide fragments that composed the protein.Applying the strategy,we provided a global picture of intra-molecular interactions of gp41 in HIV-1 infection,and identified series novel high-potent peptide HIV-1 fusion inhibitor and stable structural intermediates.Our work provided a model to study infections of other viruses using a similar mechanism.
引文
[1]Cai,L.F.;Gochin,M.;Liu,K.L.Curr Top Med Chem.2011,11:2959.
[2]Cai,L.F.;Pan,C.G.;Xu,L.;Shui,Y.;Liu,K.L.;Jiang,S.B.,FASEB J.2012,26(3):1018
[2]Cai,L.F.;Pan,C.G.;Xu,L.;Shui,Y.;Liu,K.L.;Jiang,S.B.,FASEB J.2012,26(3):1018