胆酸结合蛋白的化学蛋白质组学分析
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- 英文论文题名：Chemoproteomic Profiling of Bile-acid Interacting Proteins
- 论文作者：庄申甜 ; 李强 ; 雷晓光 ; 王初
- 英文论文作者：Shentian Zhuang ; Qiang Li ; Xiaoguang Lei ; Chu Wang ; Department of chemical biology ; Peking university
- 年：2016
- 作者机构：北京大学化学与分子工程学院;
- 论文关键词：胆酸 ; 活性探针 ; 定量蛋白质组学
- 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-第四十三分会：质谱分析
- 语种：中文
- 分类号：R3411
- 学会代码：ZGHY
- 会议名称：中国化学会第30届学术年会-第四十三分会 ; 质谱分析
- 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：180k
- 原文格式：D
- 会议级别：全国
摘要
胆酸作为重要的信号分子,参与调控肝脏内的脂质、葡萄糖和能量代谢平衡,胆酸功能障碍会引发肝脏胆汁淤积及糖尿病等相关疾病。现有的研究胆酸功能的方法主要是利用传统的细胞分子生物学技术以及基因修饰的小鼠疾病模型,进展缓慢。迄今为止还从未有在蛋白质组水平上全面发掘可以和胆酸分子相互作用的靶标蛋白的研究。本课题中我们以天然胆酸分子结构为基础设计了胆酸分子活性探针,并结合定量蛋白质组学技术,在细胞和组织水平上寻找哺乳动物体内可以和胆酸分子特异性结合的蛋白质组。实验结果显示,我们成功鉴定到胆酸转运体NTCP及核膜受体FXR以及100多个全新的潜在的胆酸结合蛋白。生物信息学分析发现,潜在胆酸靶蛋白主要集中存在于泛素-蛋白酶体降解通路、脂肪代谢、氨基酸转运和氧化还原反应过程中。
Bile acids are important signaling molecules and metabolic regulators that can regulate hepatic lipid,glucose and energy homeostasis.Disorders in bile acid metabolism are known to cause liver diseases and diabetes.However,current research in bile acid metabolism mainly relies on traditional molecular biotechnology and genetically modified mouse model.The full complement of bile acid-binding proteins in mammalian remains unexplored.Here we aim to develop a chemoproteomic strategy that uses bile acid-based probes in combination with quantitative mass spectrometry to globally profile bile acid-interacting proteins directly in proteomes from mammalian cells and tissues.In our experiments,we successfully identified endogenous bile acid transporter NTCP and receptor FXR as well as more than 100 novel bile acid-binding proteins,which are enriched in several important metabolic pathways including ubiquitin-proteasome degradation pathway,fatty acid metabolism,amino acid transport and redox regulation.
Bile acids are important signaling molecules and metabolic regulators that can regulate hepatic lipid,glucose and energy homeostasis.Disorders in bile acid metabolism are known to cause liver diseases and diabetes.However,current research in bile acid metabolism mainly relies on traditional molecular biotechnology and genetically modified mouse model.The full complement of bile acid-binding proteins in mammalian remains unexplored.Here we aim to develop a chemoproteomic strategy that uses bile acid-based probes in combination with quantitative mass spectrometry to globally profile bile acid-interacting proteins directly in proteomes from mammalian cells and tissues.In our experiments,we successfully identified endogenous bile acid transporter NTCP and receptor FXR as well as more than 100 novel bile acid-binding proteins,which are enriched in several important metabolic pathways including ubiquitin-proteasome degradation pathway,fatty acid metabolism,amino acid transport and redox regulation.
引文
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