人泛素连接酶AREL1催化结构域的晶体结构  

Crystal Structure of The Catalytic Domain of Human Ubiquitin Ligase AREL1

作　　者：李智慧 商国辉 唐晨骏 田姿姿 吴玮 陈忠周 LI Zhi-Hui;SHANG Guo-Hui;TANG Chen-Jun;TIAN Zi-Zi;WU Wei;CHEN Zhong-Zhou(Beijing Advanced Innovation Center for Food Nutrition and Human Health,College of Biological Sciences,China Agricultural University,Beijing 100193,China)

机构地区：[1]北京食品营养与人类健康高精尖创新中心,中国农业大学生物学院,北京100193

出　　处：《生物化学与生物物理进展》2020年第4期335-343,共9页Progress In Biochemistry and Biophysics

基　　金：科技部重点研发计划(2018YFE0113100);国家自然科学基金(31872713)资助项目.

摘　　要：泛素化是一种重要的翻译后修饰,几乎调控着生命活动的所有方面.泛素连接酶是泛素化过程中唯一对底物蛋白质有特异性识别能力的一类酶,它们在泛素化过程中是不可或缺的,起到非常关键的作用.人抗凋亡E3泛素连接酶(AREL1)是HECT泛素连接酶家族成员之一,它能够泛素化促凋亡蛋白SMAC、HtrA2和ARTS,并通过蛋白酶体将它们降解,从而发挥抵抗细胞凋亡的作用.本文解析了3.2?分辨率的人AREL1蛋白催化结构域(AREL1HECT)的晶体结构,并将其与HECT家族中其他成员的结构进行了比对.尺寸排阻色谱和X射线小角散射的结果表明,AREL1HECT在溶液中是以多种聚集状态形式存在的,小角散射的3D模型进一步表明AREL1HECT在溶液中会发生二聚化.这些结果将为AREL1HECT与泛素复合物结构的解析及功能的分析提供坚实的结构基础,为揭示AREL1泛素化底物蛋白质的分子机制提供重要的依据.Ubiquitination is an important post-translational modification that controls nearly every facet of a cell’s life and death.Only ubiquitin ligases E3 can specifically recognize substrates during ubiquitination,so E3 plays a pivotal role in ubiquitination and degradation of substrate proteins.Human apoptosis-resistant E3 ubiquitin protein Ligase 1(AREL1)belongs to the Homology to E6 AP C-Terminus(HECT)ubiquitin ligase family,and it inhibits apoptosis through ubiquitinating mitochondrial proapoptotic proteins such as SMAC,Htr A2,and ARTS,which are degraded by the 26 S proteasome.Here,the crystal structure of the HECT domain of AREL1(AREL1HECT)at 3.2?resolution is reported,and structural comparisons of AREL1 HECTagainst different HECT E3 ligases are conducted.Size Exclusion Chromatography(SEC)and Small Angle X-ray Scattering(SAXS)indicate that there are diverse oligomeric states of AREL1HECTin solution,and the SAXS 3 D model further suggests that AREL1HECT can dimerize in solution.These findings offer a structural basis for studying the complex of AREL1HECTand ubiquitin,and provide insights into molecular mechanisms of substrate ubiquitination by AREL1.

关 键 词：泛素化 泛素连接酶 AREL1 HECT结构域 晶体结构 二聚化 

分 类 号：Q71[生物学—分子生物学] Q5