Bax蛋白结构及相关共晶结构研究进展  

Bax protein structure and related research progress of eutectic structure

作　　者：侯沁莲 董辉[1] 杜利清[1] Hou Qinlian;Dong Hui;Du Liqing(Institute of Radiation Medicine, Chinese Academy of Medical Sciences ＆ Peking Union Medical College, 300192 Tianjin, China)

机构地区：[1]中国医学科学院北京协和医学院放射医学研究所,天津300192

出　　处：《国际生物医学工程杂志》2018年第2期187-191,共5页International Journal of Biomedical Engineering

基　　金：国家自然科学基金青年基金（31300601）;协和青年基金（33320140186,3332016144）;中国医学科学院医学与健康科技创新工程（2017-12M-3-019）

摘　　要：细胞凋亡包含多种信号通路途径,其中内在信号通路为线粒体凋亡途径,是由信号分子引起Bax等促凋亡因子活化转移至线粒体外膜形成蛋白性孔道,改变线粒体膜通透性,释放细胞色素C,激活下游caspase-9而诱导凋亡起始.针对相应使用小分子起始凋亡研究Bax结构在凋亡中结构的具体变化,结果发现,Bax蛋白结构C端S184附近有一疏水口袋结构,可结合某些小分子物质特异性去除磷酸化S184,调节Bax蛋白促进凋亡活性.目前,Bax蛋白核磁结构已获得,晶体结构未见.其与Bcl-2家族中其他蛋白形成共晶结构已有析出,可用于研究蛋白间的相互作用,了解凋亡时异源二聚体形成中具体结构、位点等的变化.旨在通过Bax核磁结构解析Bax蛋白,得到诱导细胞凋亡中位点变化从而促进凋亡起始.Apoptosis involves multiple signaling pathways. The intrinsic signaling pathway is the mitochondrial apoptotic pathway, which is caused by a series of processes. First, the pro-apoptotic factors such as Bax are activated by signaling molecules and transfer to the mitochondrial outer membrane forming protein pores, thus the mitochondrial membrane permeability is affected, and then the downstream caspase-9 is activated and the apoptosis initiation is induced by releasing cytochrome C. In order to explore the apoptosis initiation activated by small molecules, the specific structural changes of Bax in apoptosis were studied. The results showed that there is a hydrophobic pocket structure near the C-terminal S184 of the Bax protein. This structure can be combined with certain small molecular substances specifically remove phosphorylation S184, and regulate Bax protein to promote apoptosis activity. At present, the nuclear magnetic structure of Bax protein has been obtained and the crystal structure has not been revealed. The eutectic structure formed by corresponding with other proteins in the Bcl-2 family has been resolved, which can be used to study the interactions between proteins and to understand the specific structural changes in the formation of heterologous dimers during apoptosis, site changes, etc. In this paper, the Bax protein structure resolved by nuclear magnetic structure was reviewed to learn the change of the sites in the induced apoptosis so as to promote the research on apoptosis initiation.

关 键 词：BAX蛋白 Bax蛋白结构 蛋白晶体结构 

分 类 号：Q51[生物学—生物化学]