盘基网柄菌早衰蛋白结构与功能生物信息学分析
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摘要
早衰蛋白(presenilin, PS)是γ分泌酶的组成成分,其突变可造成阿尔兹海默病(Alzheimer disease,AD)的形成。因PS所造成AD的发病机理较复杂,因而我们想探究一下模式生物盘基网柄菌(Dictyostelium discoideum)是否能够作为研究早衰蛋白的模型。从NCBI网站中得到盘基网柄菌早衰蛋白DdPsenA和DdPsenB氨基酸序列,随后利用ProtScale、ProtParam理化性分析工具、保守结构域、TMHMM2跨膜区分析网站、进化树软件MEGA6.0、二级结构PredictProtein以及三级结构SWISS-Model服务器对上述蛋白进行生物信息学分析。DdPsenA的氨基酸长度为622,是亲水性蛋白,其相对分子质量为69 502.79,等电点为4.53。DdPsenB的氨基酸长度为473,属于疏水性蛋白,其相对分子质量为52 558.74,等电点为4.49,与DdPsenA同属于Peptidase_A22B超家族。跨膜分析出DdPsenA和DdPsenB均有8个跨膜区。DdPsenA与人类presenilin-2序列相似性为67%,Dd PsenB与人类presenilin-1序列相似性分别为60%。盘基网柄菌可以作为研究早衰蛋白功能和作用机制的模型。
Presenilin(PS) is a component of γ-secretase, which mutation can cause the formation of Alzheimer's disease(AD). Because the pathogenesis of AD caused by PS is more complex, we want to explore whether the model organism D. discoideum can be a model to study presenilin. The amino acid sequences of D. discoideum presenilins DdPsenA and DdPsenB were obtained from the NCBI website. Then we carried out the bioinformatics analyses of DdPsenA and Dd PsenB by ProtScale, ProtParam, conserved domain, TMHMM2, MEGA6.0, PredictProtein and SWISS-Model. The amino acid length of DdPsenA is 622, which is a hydrophilic protein with a relative molecular mass of 69 502.79 and an isoelectric point of 4.53. The amino acid length of DdPsenB is 473, which is a hydrophobic protein with a relative molecular mass of 52 558.74 and an isoelectric point of 4.49, belonging to Peptidase_A22 B super family as well as DdPsenA. DdPsenA and DdPsenB have eight transmembrane regions. The similarity of DdPsenA with presenilin-2 is 67%. The similarity of DdPsenB with presenilin-1 is 60%. D. discoideum can be used as a model for the investigation of the function and mechanism of presenilin.
Presenilin(PS) is a component of γ-secretase, which mutation can cause the formation of Alzheimer's disease(AD). Because the pathogenesis of AD caused by PS is more complex, we want to explore whether the model organism D. discoideum can be a model to study presenilin. The amino acid sequences of D. discoideum presenilins DdPsenA and DdPsenB were obtained from the NCBI website. Then we carried out the bioinformatics analyses of DdPsenA and Dd PsenB by ProtScale, ProtParam, conserved domain, TMHMM2, MEGA6.0, PredictProtein and SWISS-Model. The amino acid length of DdPsenA is 622, which is a hydrophilic protein with a relative molecular mass of 69 502.79 and an isoelectric point of 4.53. The amino acid length of DdPsenB is 473, which is a hydrophobic protein with a relative molecular mass of 52 558.74 and an isoelectric point of 4.49, belonging to Peptidase_A22 B super family as well as DdPsenA. DdPsenA and DdPsenB have eight transmembrane regions. The similarity of DdPsenA with presenilin-2 is 67%. The similarity of DdPsenB with presenilin-1 is 60%. D. discoideum can be used as a model for the investigation of the function and mechanism of presenilin.
引文
Bai X.C.,Yan C.Y.,Yang G.H.,Lu P.L.,Ma D.,Sun L.F.,Zhou R.,Scheres S.H.W.,and Shi Y.G.,2015,An atomic structure of humanγ-secretase,Nature,525(7568):212-217
Deng Y.,Tarassishin L.,Kallhoff V.,Peethumnongsin E.,Wu L.,Li Y.M.,and Zheng H.,2006,Deletion of presenilin 1 hydrophilic loop sequence leads to impairedγ-secretase activity and exacerbated amyloid pathology,The Journal of Neuroscience,26(14):3845-3854
De Strooper B.,and Annaert W.,2010,Novel research horizons for presenilins andγ-secretases in cell biology and disease,Annual Review of Cell and Developmental Biology,26:235-260
De Strooper B.,Iwatsubo T.,and Wolfe M.S.,2012,Presenilins andγ-secretase:structure,function,and role in Alzheimer disease,Cold Spring Harbor Perspectives in Medicine,2(1):a006304
Li L.H.,Tu Q.Y.,Deng X.H.,Xia J.,Hou D.R.,Guo K.,and Zi X.H.,2017,Mutant presenilin2 promotes apoptosis through the p53/mi R-34a axis in neuronal cells,Brain Research,1662:57-64
Nie J.,and Shi J.S.,2017,A role for presenilin in the mechanism of Alzheimer's disease,Huaxi Yaoxue Zazhi(West China Journal of Pharmaceutical Sciences),32(1):99-103(聂晶,石京山,2017,早老素在阿尔茨海默病发病机制中的作用,华西药学杂志,32(1):99-103)
Sun J.C.,and Hou L.S.,2011,Subcellular localization of allantoicase in Dictyostelium discoideum cells during differentiation and apoptosis,Zhongguo Xibao Shengwuxue Xuebao(Chinese Journal of Cell Biology),33(8):880-885(孙进楚,侯连生,2011,盘基网柄菌细胞发育过程中尿囊酸酶的亚细胞定位,中国细胞生物学学报,33(8):880-885)
Singh S.,Mohamed W.,Aguessy A.,Dyett E.,Shah S.,Khan M.,Baskar R.,and Brazil D.,2017,Functional interaction of PkcA and PIdB regulate aggregation and development in Dictyostelium discoideum,Cellular Signalling,34:47-54
Uemura K.,Lill C.M.,Li X.J.,Peters J.A.,Ivanov A.,Fan Z.Y.,De Strooper B.,Bacskai B.J.,Hyman B.T.,and Berezovska O.,2009,Allosteric modulation of PS1/γ-secretase conformation correlates with amyloidβ42/40 ratio,PLoS One,4(11):e7893
Williams R.S.B.,Boeckeler K.,Gr覿f R.,Müller-Taubenberger A.,Li Z.R.,Isberg R.R.,Wessels D.,Soll D.R.,Alexander H.,and Alexander S.,2006,Towards a molecular understanding of human diseases using Dictyostelium discoideum,Trends in Molecular Medicine,12(9):415-424
Wang D.L.,and Wang J.Z.,2003,Presenilin and Alzheimer's disease,Shengming De Huaxue(Chemistry of Life),23(6):416-418(王丹玲,王建枝,2003,早老素与阿尔茨海默病,生命的化学,23(6):416-418)
Xue D.M.,and Liu D.D.,2015,Advances on the developmental mechanism of Dictyostelium discoideum,Shengwu Jishu(Biotechnology),25(5):500-504(薛德明,刘丹丹,2015,盘基网柄菌发育机制研究进展,生物技术,25(5):500-504)
Zhai Z.H.,Wang X.Z.,and Ding M.X.,eds.,2016,Cell biology,The fourth edition,Higher Education Press,Beijing,China,pp.352-341(翟中和,王喜忠,丁明孝,主编,2016,细胞生物学,第4版,高等教育出版社,中国,北京,pp.352-341)
Zeng L.L.,Hu C.,Zhang F.Q.,Xu D.C.,Cui M.Z.,and Xu X.,2015,Cellular FLICE-like inhibitory protein(c-FLIP)and PS1-associated protein(PSAP)mediate presenilin 1-inducedγ-secretase-dependent and independent apoptosis,respectively,The Journal of Biological Chemistry,290(30):18269-18280
Deng Y.,Tarassishin L.,Kallhoff V.,Peethumnongsin E.,Wu L.,Li Y.M.,and Zheng H.,2006,Deletion of presenilin 1 hydrophilic loop sequence leads to impairedγ-secretase activity and exacerbated amyloid pathology,The Journal of Neuroscience,26(14):3845-3854
De Strooper B.,and Annaert W.,2010,Novel research horizons for presenilins andγ-secretases in cell biology and disease,Annual Review of Cell and Developmental Biology,26:235-260
De Strooper B.,Iwatsubo T.,and Wolfe M.S.,2012,Presenilins andγ-secretase:structure,function,and role in Alzheimer disease,Cold Spring Harbor Perspectives in Medicine,2(1):a006304
Li L.H.,Tu Q.Y.,Deng X.H.,Xia J.,Hou D.R.,Guo K.,and Zi X.H.,2017,Mutant presenilin2 promotes apoptosis through the p53/mi R-34a axis in neuronal cells,Brain Research,1662:57-64
Nie J.,and Shi J.S.,2017,A role for presenilin in the mechanism of Alzheimer's disease,Huaxi Yaoxue Zazhi(West China Journal of Pharmaceutical Sciences),32(1):99-103(聂晶,石京山,2017,早老素在阿尔茨海默病发病机制中的作用,华西药学杂志,32(1):99-103)
Sun J.C.,and Hou L.S.,2011,Subcellular localization of allantoicase in Dictyostelium discoideum cells during differentiation and apoptosis,Zhongguo Xibao Shengwuxue Xuebao(Chinese Journal of Cell Biology),33(8):880-885(孙进楚,侯连生,2011,盘基网柄菌细胞发育过程中尿囊酸酶的亚细胞定位,中国细胞生物学学报,33(8):880-885)
Singh S.,Mohamed W.,Aguessy A.,Dyett E.,Shah S.,Khan M.,Baskar R.,and Brazil D.,2017,Functional interaction of PkcA and PIdB regulate aggregation and development in Dictyostelium discoideum,Cellular Signalling,34:47-54
Uemura K.,Lill C.M.,Li X.J.,Peters J.A.,Ivanov A.,Fan Z.Y.,De Strooper B.,Bacskai B.J.,Hyman B.T.,and Berezovska O.,2009,Allosteric modulation of PS1/γ-secretase conformation correlates with amyloidβ42/40 ratio,PLoS One,4(11):e7893
Williams R.S.B.,Boeckeler K.,Gr覿f R.,Müller-Taubenberger A.,Li Z.R.,Isberg R.R.,Wessels D.,Soll D.R.,Alexander H.,and Alexander S.,2006,Towards a molecular understanding of human diseases using Dictyostelium discoideum,Trends in Molecular Medicine,12(9):415-424
Wang D.L.,and Wang J.Z.,2003,Presenilin and Alzheimer's disease,Shengming De Huaxue(Chemistry of Life),23(6):416-418(王丹玲,王建枝,2003,早老素与阿尔茨海默病,生命的化学,23(6):416-418)
Xue D.M.,and Liu D.D.,2015,Advances on the developmental mechanism of Dictyostelium discoideum,Shengwu Jishu(Biotechnology),25(5):500-504(薛德明,刘丹丹,2015,盘基网柄菌发育机制研究进展,生物技术,25(5):500-504)
Zhai Z.H.,Wang X.Z.,and Ding M.X.,eds.,2016,Cell biology,The fourth edition,Higher Education Press,Beijing,China,pp.352-341(翟中和,王喜忠,丁明孝,主编,2016,细胞生物学,第4版,高等教育出版社,中国,北京,pp.352-341)
Zeng L.L.,Hu C.,Zhang F.Q.,Xu D.C.,Cui M.Z.,and Xu X.,2015,Cellular FLICE-like inhibitory protein(c-FLIP)and PS1-associated protein(PSAP)mediate presenilin 1-inducedγ-secretase-dependent and independent apoptosis,respectively,The Journal of Biological Chemistry,290(30):18269-18280