自噬标志分子ATG8同源蛋白的生物信息
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摘要
自噬是细胞重要的代谢途径,ATG8在自噬体形成过程中起着重要的作用。对ATG8蛋白进行生物信息学分析研究十分必要。本研究以NCBI中人ATG8同源蛋白序列数据为研究材料,分析其与10种模式生物间基因拷贝数、氨基酸序列、蛋白质保守位点相关性。结果表明,人6种ATG8同源蛋白分别定位于5条染色体上,均有泛素样GABARAP结构域。并且,所有模式生物的ATG8同源蛋白中N-端氨基酸序列保守性强于C-端序列。本研究构建的ATG8同源蛋白系统发育树显示,人的ATG8同源蛋白与脊椎动物(斑马鱼,爪蟾,小鼠,大鼠,牛)的ATG8蛋白亲缘关系更近,人的GABARAPs与酵母的ATG8蛋白与的亲缘关系较近。本研究为研究细胞自噬过程及机制提供了丰富的生物进化和生物信息数据支持。
Autophagy is an important metabolic pathway in cells, and ATG8 plays an important role in the formation of autophagosomes. It is necessary to study the bioinformatical analysis of ATG8 protein. In this study,we took the data of human ATG8 homologous protein in NCBI as the research material, aiming to analyze the correlations of gene copy number, amino acid sequence and protein conserved sites between human ATG8 homologous protein and other 10 model organisms. The results showed that 6 ATG8 homologous proteins in human were located in 5 chromosomes, and all of which contain the ubiquitin like GABARAP domain. Moreover,the N-terminal amino acid sequence of all ATG8 homologous proteins in all model organisms is more conserved than that of the sequence of C-end sequence. The phylogenetic tree of the ATG8 homologous protein constructed in this study showed that phylogenetic relationship of human ATG8 homologous proteins was similar with vertebrates(such as Danio rerio, Xenopus laevis, Mus musculus, Rattus norvegicus, Bos taurus), and the phylogenetic relationship between human GABARAPs and yeast ATG8 protein was close. This study provided abundant data of biological evolution and information to further study the mechanism of autophagy.
Autophagy is an important metabolic pathway in cells, and ATG8 plays an important role in the formation of autophagosomes. It is necessary to study the bioinformatical analysis of ATG8 protein. In this study,we took the data of human ATG8 homologous protein in NCBI as the research material, aiming to analyze the correlations of gene copy number, amino acid sequence and protein conserved sites between human ATG8 homologous protein and other 10 model organisms. The results showed that 6 ATG8 homologous proteins in human were located in 5 chromosomes, and all of which contain the ubiquitin like GABARAP domain. Moreover,the N-terminal amino acid sequence of all ATG8 homologous proteins in all model organisms is more conserved than that of the sequence of C-end sequence. The phylogenetic tree of the ATG8 homologous protein constructed in this study showed that phylogenetic relationship of human ATG8 homologous proteins was similar with vertebrates(such as Danio rerio, Xenopus laevis, Mus musculus, Rattus norvegicus, Bos taurus), and the phylogenetic relationship between human GABARAPs and yeast ATG8 protein was close. This study provided abundant data of biological evolution and information to further study the mechanism of autophagy.
引文
Choi A.M.,Ryter S.W.,and Levine B.,2013,Autophagy in human health and disease,New England Journal of Medicine,368(7):651-652
Guo M.F.,Gao J.R.,Jiang H.,Shan L.,Wei L.B.,Fang C.H.,Qin X.J.,Dai Y.J.,and Jiang N.N.,2017,Screening and bioin formatic analysis of genes related to lipid metabolism in liver of rats with type 2 diabetes mellitus,Zhongguo Shengwu Huaxue Yu Fenzi Shengwu Xuebao(Chinese Journal of Biochemistry and Molecular Biology),33(7):726-735(郭明飞,高家荣,姜辉,单莉,魏良兵,方朝辉,秦秀娟,戴雅吉,姜楠楠,2017,2型糖尿病模型大鼠肝脂代谢相关基因的筛选及生物信息学分析,中国生物化学与分子生物学报,33(7):726-735)
Huang R.,and Liu W.,2015,Identifying an essential role of nuclear LC3 for autophagy,Autophagy,11(5):852-853
Lamb C.A.,Yoshimori T.,and Tooze S.A.,2013,The autophagosome:origins unknown,biogenesis complex,Nature Reviews Molecular Cell Biology,14(12):759-774
Lapaquette P.,Guzzo J.,Bretillon L.,and Bringer M.A.,2015,Cellular and molecular connections between autophagy and inflammation,Mediators of Inflammation,2015:398483
Lee Y.K.,and Lee J.A.,2016,Role of the mammalian ATG8/LC3family in autophagy:differential and compensatory roles in the spatiotemporal regulation of autophagy,BMB Reports49(8):424-430
Li C.,Fu X.Z.,Li N.Q.,and Lin Q.,2015,Eradication or hijack autophagy interactions and virus infection,Jiyinzuxue Yu Yingyong Shengwuxue(Genomics and Applied Biology)34(11):2345-2350(李趁,付小哲,李宁求,林强,2015,清除或劫持:细胞自噬与病毒感染,基因组学与应用生物学,34(11):2345-2350)
Liang R.Y.,Chen X.Y.,Sun S.H.,Sun H.X.,and Guo W.T.2017,Bioinformatics analysis of TFAM gene encoding protein in sheep,Jiyinzuxue Yu Yingyong Shengwuxue(Genomics and Applied Biology),36(2):575-581(梁瑞圆,陈晓勇,孙少华,孙洪新,郭伟涛,2017,绵羊TFAM基因编码蛋白生物信息学分析,基因组学与应用生物学,36(2)575-581)
Lópezotín C.,Blasco M.A.,Partridge L.,Serrano M.,and Kroemer G.,2013,The hallmarks of aging,Cell,153(6):1194-1217
Nakatogawa H.Y.,Ichimura Y.,and Ohsumi Y.,2007,Atg8,a ubiquitin-like protein required for autophagosome formation mediates membrane tethering and hemifusion,Cell,130(1)165-178
Nguyen T.N.,Padman B.S.,Usher J.,Oorschot V.,Ramm G.and Lazarou M.,2016,Atg8 family LC3/GABARAP proteins are crucial for autophagosome-lysosome fusion but no autophagosome formation during PINK1/Parkin mitophagy and starvation,Journal of Cell Biology,215(6):857-874
Ryabovol V.V.,and Minibayeva F.V.,2016,Molecular mechanisms of autophagy in plants:role of ATG8 proteins in formation and functioning of autophagosomes,Biochemistry Biolhimiia,81(4):348-363
Shpilka T.,Weidberg H.,Pietrokovski S.,and Elazar Z.,2011,Atg8:an autophagy-related ubiquitin-like protein family,Genome Biology,12(7):226
Wang Y.H.,Xia S.Y.,Wang F.,and Zhang L.,2015,The latest progress of the relationship between m TOR,beclin 1 and tumor in autophagy pathway,Jiyinzuxue Yu Yingyong Shengwuxue(Genomics and Applied Biology),34(8):1656-1662(王远航,夏盛源,王芳,张岚,2015,自噬通路中m TOR,Beclin1与肿瘤关系研究的最新进展,基因组学与应用生物学,34(8):1656-1662)
Wang S.H.,Jia Z.Y.,Li C.T.,and Shi L.Y.,2017,Cloning and bioinformatics analysis of ORF83 gene in dandong srain in koi herpes virus,Jiyinzuxue Yu Yingyong Shengwuxue(Ge nomics and Applied Biology),36(4):1451-1461(王世会,贾智英,李池陶,石连玉,2017,锦鲤疱疹病毒丹东株ORF83基因克隆及生物信息学分析,基因组学与应用生物学,36(4):1451-1461)
Weidberg H.,Shvets E.,Shpilka T.,Shimron F.,Shinder V.,and Elazar Z.,2010,LC3 and GATE-16/GABARAP subfamilies are both essential yet act differently in autophagosome biogenesis,EMBO Journal,29(11):1792-1802
Xie Z.,Nair U.,and Klionsky D.J.,2008,Atg8 controls phagophore expansion during autophagosome formation,Molecular and Cellular Biology,19:3290-3298
Zheng Z.G.,and Zhang P.H.,2016,Advances in the molecular mechansim of autophagy formation,Zhongguo Xibao Shengwuxue Xuebao(Chinese Journal of Cell Biology),38(12):1541-1548(郑祖国,张评浒,2016,细胞自噬形成机制及其功能研究进展,中国细胞生物学学报,38(12):1541-1548)
Guo M.F.,Gao J.R.,Jiang H.,Shan L.,Wei L.B.,Fang C.H.,Qin X.J.,Dai Y.J.,and Jiang N.N.,2017,Screening and bioin formatic analysis of genes related to lipid metabolism in liver of rats with type 2 diabetes mellitus,Zhongguo Shengwu Huaxue Yu Fenzi Shengwu Xuebao(Chinese Journal of Biochemistry and Molecular Biology),33(7):726-735(郭明飞,高家荣,姜辉,单莉,魏良兵,方朝辉,秦秀娟,戴雅吉,姜楠楠,2017,2型糖尿病模型大鼠肝脂代谢相关基因的筛选及生物信息学分析,中国生物化学与分子生物学报,33(7):726-735)
Huang R.,and Liu W.,2015,Identifying an essential role of nuclear LC3 for autophagy,Autophagy,11(5):852-853
Lamb C.A.,Yoshimori T.,and Tooze S.A.,2013,The autophagosome:origins unknown,biogenesis complex,Nature Reviews Molecular Cell Biology,14(12):759-774
Lapaquette P.,Guzzo J.,Bretillon L.,and Bringer M.A.,2015,Cellular and molecular connections between autophagy and inflammation,Mediators of Inflammation,2015:398483
Lee Y.K.,and Lee J.A.,2016,Role of the mammalian ATG8/LC3family in autophagy:differential and compensatory roles in the spatiotemporal regulation of autophagy,BMB Reports49(8):424-430
Li C.,Fu X.Z.,Li N.Q.,and Lin Q.,2015,Eradication or hijack autophagy interactions and virus infection,Jiyinzuxue Yu Yingyong Shengwuxue(Genomics and Applied Biology)34(11):2345-2350(李趁,付小哲,李宁求,林强,2015,清除或劫持:细胞自噬与病毒感染,基因组学与应用生物学,34(11):2345-2350)
Liang R.Y.,Chen X.Y.,Sun S.H.,Sun H.X.,and Guo W.T.2017,Bioinformatics analysis of TFAM gene encoding protein in sheep,Jiyinzuxue Yu Yingyong Shengwuxue(Genomics and Applied Biology),36(2):575-581(梁瑞圆,陈晓勇,孙少华,孙洪新,郭伟涛,2017,绵羊TFAM基因编码蛋白生物信息学分析,基因组学与应用生物学,36(2)575-581)
Lópezotín C.,Blasco M.A.,Partridge L.,Serrano M.,and Kroemer G.,2013,The hallmarks of aging,Cell,153(6):1194-1217
Nakatogawa H.Y.,Ichimura Y.,and Ohsumi Y.,2007,Atg8,a ubiquitin-like protein required for autophagosome formation mediates membrane tethering and hemifusion,Cell,130(1)165-178
Nguyen T.N.,Padman B.S.,Usher J.,Oorschot V.,Ramm G.and Lazarou M.,2016,Atg8 family LC3/GABARAP proteins are crucial for autophagosome-lysosome fusion but no autophagosome formation during PINK1/Parkin mitophagy and starvation,Journal of Cell Biology,215(6):857-874
Ryabovol V.V.,and Minibayeva F.V.,2016,Molecular mechanisms of autophagy in plants:role of ATG8 proteins in formation and functioning of autophagosomes,Biochemistry Biolhimiia,81(4):348-363
Shpilka T.,Weidberg H.,Pietrokovski S.,and Elazar Z.,2011,Atg8:an autophagy-related ubiquitin-like protein family,Genome Biology,12(7):226
Wang Y.H.,Xia S.Y.,Wang F.,and Zhang L.,2015,The latest progress of the relationship between m TOR,beclin 1 and tumor in autophagy pathway,Jiyinzuxue Yu Yingyong Shengwuxue(Genomics and Applied Biology),34(8):1656-1662(王远航,夏盛源,王芳,张岚,2015,自噬通路中m TOR,Beclin1与肿瘤关系研究的最新进展,基因组学与应用生物学,34(8):1656-1662)
Wang S.H.,Jia Z.Y.,Li C.T.,and Shi L.Y.,2017,Cloning and bioinformatics analysis of ORF83 gene in dandong srain in koi herpes virus,Jiyinzuxue Yu Yingyong Shengwuxue(Ge nomics and Applied Biology),36(4):1451-1461(王世会,贾智英,李池陶,石连玉,2017,锦鲤疱疹病毒丹东株ORF83基因克隆及生物信息学分析,基因组学与应用生物学,36(4):1451-1461)
Weidberg H.,Shvets E.,Shpilka T.,Shimron F.,Shinder V.,and Elazar Z.,2010,LC3 and GATE-16/GABARAP subfamilies are both essential yet act differently in autophagosome biogenesis,EMBO Journal,29(11):1792-1802
Xie Z.,Nair U.,and Klionsky D.J.,2008,Atg8 controls phagophore expansion during autophagosome formation,Molecular and Cellular Biology,19:3290-3298
Zheng Z.G.,and Zhang P.H.,2016,Advances in the molecular mechansim of autophagy formation,Zhongguo Xibao Shengwuxue Xuebao(Chinese Journal of Cell Biology),38(12):1541-1548(郑祖国,张评浒,2016,细胞自噬形成机制及其功能研究进展,中国细胞生物学学报,38(12):1541-1548)