IntAct European Bioinformatics Institute IntAct intact http://www.ebi.ac.uk/ http://www.ebi.ac.uk/intact/query/${ac} EBI-[0-9]+|IA:[0-9]+ INTerAction database (IntAct) provides an open source database and toolkit for the storage, presentation and analysis of molecular interactions. http://www.ebi.ac.uk/intact European Bioinformatics Institute; Wellcome Trust Genome Campus; Hinxton, Cambridge; CB10 1SD; United Kingdom http://www.ebi.ac.uk/intact/ Protein disulfide isomerase interacts with tau protein and inhibits its fibrillization. Protein disulfide isomerase interacts with tau protein and inhibits its fibrillization. PloS one 2013 imex curation Li-Rong Xu, Xiao-Ling Liu, Jie Chen,Yi Liang, Xu LR., Liu XL., Chen J., Liang Y., Xu LR., Liu XL., Chen J., Liang Y. Neurodegeneration - Publications depicting interactions involved in neurodegenerative diseases. Parkinsons - Interactions investigated in the context of Parkinsons disease Alzheimers - Interactions investigated in the context of Alzheimers disease Thioflavin T binding assay:-When ThT binds to beta sheet-rich structures, the dye displays enhanced fluorescence and a characteristic red shift of its emission spectrum. ThT is used as a dye to visualize and quantify the presence or fibrilization of misfolded protein aggregates. Tau 40 corresponds to 2N4R Tau which has 441 amino acids. PDI domain numbering was taken from Wang-2012 (PMID:22090031) which references several articles by LW Ruddock, donor of the PDI fragments. liangyi@whu.edu.cn 13-Jan-2014: Contacted by IntAct-Help. Only protein-protein interactions in vitro In vitro fluorescence spectr classical fluorescence spectroscopy fluorescence spectr predetermined predetermined participant predetermined Li-Rong Xu, Xiao-Ling Liu, Jie Chen, Yi Liang Neurodegeneration - Publications depicting interactions involved in neurodegenerative diseases. Thioflavin T binding assay:-When ThT binds to beta sheet-rich structures, the dye displays enhanced fluorescence and a characteristic red shift of its emission spectrum. ThT is used as a dye to visualize and quantify the presence or fibrilization of misfolded protein aggregates. Tau 40 corresponds to 2N4R Tau which has 441 amino acids. PDI domain numbering was taken from Wang-2012 (PMID:22090031) which references several articles by LW Ruddock, donor of the PDI fragments. liangyi@whu.edu.cn Accepted 2013-NOV-28 by PPORRAS Plos One 2013 Only protein-protein interactions imex curation Protein disulfide isomerase interacts with tau protein and inhibits its fibrillization. Protein disulfide isomerase interacts with tau protein and inhibits its fibrillization. PloS one 2013 imex curation Li-Rong Xu, Xiao-Ling Liu, Jie Chen,Yi Liang, Xu LR., Liu XL., Chen J., Liang Y., Xu LR., Liu XL., Chen J., Liang Y. Neurodegeneration - Publications depicting interactions involved in neurodegenerative diseases. Parkinsons - Interactions investigated in the context of Parkinsons disease Alzheimers - Interactions investigated in the context of Alzheimers disease Thioflavin T binding assay:-When ThT binds to beta sheet-rich structures, the dye displays enhanced fluorescence and a characteristic red shift of its emission spectrum. ThT is used as a dye to visualize and quantify the presence or fibrilization of misfolded protein aggregates. Tau 40 corresponds to 2N4R Tau which has 441 amino acids. PDI domain numbering was taken from Wang-2012 (PMID:22090031) which references several articles by LW Ruddock, donor of the PDI fragments. liangyi@whu.edu.cn 13-Jan-2014: Contacted by IntAct-Help. Only protein-protein interactions in vitro In vitro itc isothermal titration calorimetry ITC ITC itc predetermined predetermined participant predetermined Li-Rong Xu, Xiao-Ling Liu, Jie Chen, Yi Liang Neurodegeneration - Publications depicting interactions involved in neurodegenerative diseases. Thioflavin T binding assay:-When ThT binds to beta sheet-rich structures, the dye displays enhanced fluorescence and a characteristic red shift of its emission spectrum. ThT is used as a dye to visualize and quantify the presence or fibrilization of misfolded protein aggregates. Tau 40 corresponds to 2N4R Tau which has 441 amino acids. PDI domain numbering was taken from Wang-2012 (PMID:22090031) which references several articles by LW Ruddock, donor of the PDI fragments. liangyi@whu.edu.cn Accepted 2013-NOV-28 by PPORRAS Plos One 2013 Only protein-protein interactions imex curation Protein disulfide isomerase interacts with tau protein and inhibits its fibrillization. Protein disulfide isomerase interacts with tau protein and inhibits its fibrillization. PloS one 2013 imex curation Li-Rong Xu, Xiao-Ling Liu, Jie Chen,Yi Liang, Xu LR., Liu XL., Chen J., Liang Y., Xu LR., Liu XL., Chen J., Liang Y. Neurodegeneration - Publications depicting interactions involved in neurodegenerative diseases. Parkinsons - Interactions investigated in the context of Parkinsons disease Alzheimers - Interactions investigated in the context of Alzheimers disease Thioflavin T binding assay:-When ThT binds to beta sheet-rich structures, the dye displays enhanced fluorescence and a characteristic red shift of its emission spectrum. ThT is used as a dye to visualize and quantify the presence or fibrilization of misfolded protein aggregates. Tau 40 corresponds to 2N4R Tau which has 441 amino acids. PDI domain numbering was taken from Wang-2012 (PMID:22090031) which references several articles by LW Ruddock, donor of the PDI fragments. liangyi@whu.edu.cn 13-Jan-2014: Contacted by IntAct-Help. Only protein-protein interactions in vitro In vitro solution sedimentati cosedimentation in solution solution sedimentati weight silver stain molecular weight estimation by silver staining weight silver stain Li-Rong Xu, Xiao-Ling Liu, Jie Chen, Yi Liang Neurodegeneration - Publications depicting interactions involved in neurodegenerative diseases. Thioflavin T binding assay:-When ThT binds to beta sheet-rich structures, the dye displays enhanced fluorescence and a characteristic red shift of its emission spectrum. ThT is used as a dye to visualize and quantify the presence or fibrilization of misfolded protein aggregates. Tau 40 corresponds to 2N4R Tau which has 441 amino acids. PDI domain numbering was taken from Wang-2012 (PMID:22090031) which references several articles by LW Ruddock, donor of the PDI fragments. liangyi@whu.edu.cn Accepted 2013-NOV-28 by PPORRAS Plos One 2013 Only protein-protein interactions imex curation Protein disulfide isomerase interacts with tau protein and inhibits its fibrillization. Protein disulfide isomerase interacts with tau protein and inhibits its fibrillization. PloS one 2013 imex curation Li-Rong Xu, Xiao-Ling Liu, Jie Chen,Yi Liang, Xu LR., Liu XL., Chen J., Liang Y., Xu LR., Liu XL., Chen J., Liang Y. Neurodegeneration - Publications depicting interactions involved in neurodegenerative diseases. Parkinsons - Interactions investigated in the context of Parkinsons disease Alzheimers - Interactions investigated in the context of Alzheimers disease Thioflavin T binding assay:-When ThT binds to beta sheet-rich structures, the dye displays enhanced fluorescence and a characteristic red shift of its emission spectrum. ThT is used as a dye to visualize and quantify the presence or fibrilization of misfolded protein aggregates. Tau 40 corresponds to 2N4R Tau which has 441 amino acids. PDI domain numbering was taken from Wang-2012 (PMID:22090031) which references several articles by LW Ruddock, donor of the PDI fragments. liangyi@whu.edu.cn 13-Jan-2014: Contacted by IntAct-Help. Only protein-protein interactions human-sh_sy5y Homo sapiens SH-SY5Y cell line sh_sy5y Human neuroblastoma cells confocal microscopy confocal microscopy immunocytochemistry immunocytochemistry Li-Rong Xu, Xiao-Ling Liu, Jie Chen, Yi Liang Neurodegeneration - Publications depicting interactions involved in neurodegenerative diseases. Thioflavin T binding assay:-When ThT binds to beta sheet-rich structures, the dye displays enhanced fluorescence and a characteristic red shift of its emission spectrum. ThT is used as a dye to visualize and quantify the presence or fibrilization of misfolded protein aggregates. Tau 40 corresponds to 2N4R Tau which has 441 amino acids. PDI domain numbering was taken from Wang-2012 (PMID:22090031) which references several articles by LW Ruddock, donor of the PDI fragments. liangyi@whu.edu.cn Accepted 2013-NOV-28 by PPORRAS Plos One 2013 Only protein-protein interactions imex curation Protein disulfide isomerase interacts with tau protein and inhibits its fibrillization. Protein disulfide isomerase interacts with tau protein and inhibits its fibrillization. PloS one 2013 imex curation Li-Rong Xu, Xiao-Ling Liu, Jie Chen,Yi Liang, Xu LR., Liu XL., Chen J., Liang Y., Xu LR., Liu XL., Chen J., Liang Y. Neurodegeneration - Publications depicting interactions involved in neurodegenerative diseases. Parkinsons - Interactions investigated in the context of Parkinsons disease Alzheimers - Interactions investigated in the context of Alzheimers disease Thioflavin T binding assay:-When ThT binds to beta sheet-rich structures, the dye displays enhanced fluorescence and a characteristic red shift of its emission spectrum. ThT is used as a dye to visualize and quantify the presence or fibrilization of misfolded protein aggregates. Tau 40 corresponds to 2N4R Tau which has 441 amino acids. PDI domain numbering was taken from Wang-2012 (PMID:22090031) which references several articles by LW Ruddock, donor of the PDI fragments. liangyi@whu.edu.cn 13-Jan-2014: Contacted by IntAct-Help. Only protein-protein interactions in vitro In vitro electron microscopy electron microscopy Electron crystallography Electron cryomicroscopy Electron crystallography Electron cryomicroscopy predetermined predetermined participant predetermined Li-Rong Xu, Xiao-Ling Liu, Jie Chen, Yi Liang Neurodegeneration - Publications depicting interactions involved in neurodegenerative diseases. Thioflavin T binding assay:-When ThT binds to beta sheet-rich structures, the dye displays enhanced fluorescence and a characteristic red shift of its emission spectrum. ThT is used as a dye to visualize and quantify the presence or fibrilization of misfolded protein aggregates. Tau 40 corresponds to 2N4R Tau which has 441 amino acids. PDI domain numbering was taken from Wang-2012 (PMID:22090031) which references several articles by LW Ruddock, donor of the PDI fragments. liangyi@whu.edu.cn Accepted 2013-NOV-28 by PPORRAS Plos One 2013 Only protein-protein interactions imex curation Protein disulfide isomerase interacts with tau protein and inhibits its fibrillization. Protein disulfide isomerase interacts with tau protein and inhibits its fibrillization. PloS one 2013 imex curation Li-Rong Xu, Xiao-Ling Liu, Jie Chen,Yi Liang, Xu LR., Liu XL., Chen J., Liang Y., Xu LR., Liu XL., Chen J., Liang Y. Neurodegeneration - Publications depicting interactions involved in neurodegenerative diseases. Parkinsons - Interactions investigated in the context of Parkinsons disease Alzheimers - Interactions investigated in the context of Alzheimers disease Thioflavin T binding assay:-When ThT binds to beta sheet-rich structures, the dye displays enhanced fluorescence and a characteristic red shift of its emission spectrum. ThT is used as a dye to visualize and quantify the presence or fibrilization of misfolded protein aggregates. Tau 40 corresponds to 2N4R Tau which has 441 amino acids. PDI domain numbering was taken from Wang-2012 (PMID:22090031) which references several articles by LW Ruddock, donor of the PDI fragments. liangyi@whu.edu.cn 13-Jan-2014: Contacted by IntAct-Help. Only protein-protein interactions human-sh_sy5y Homo sapiens SH-SY5Y cell line sh_sy5y Human neuroblastoma cells anti tag coip anti tag coimmunoprecipitation anti tag coip western blot western blot Immuno blot Immuno blot Li-Rong Xu, Xiao-Ling Liu, Jie Chen, Yi Liang Neurodegeneration - Publications depicting interactions involved in neurodegenerative diseases. Thioflavin T binding assay:-When ThT binds to beta sheet-rich structures, the dye displays enhanced fluorescence and a characteristic red shift of its emission spectrum. ThT is used as a dye to visualize and quantify the presence or fibrilization of misfolded protein aggregates. Tau 40 corresponds to 2N4R Tau which has 441 amino acids. PDI domain numbering was taken from Wang-2012 (PMID:22090031) which references several articles by LW Ruddock, donor of the PDI fragments. liangyi@whu.edu.cn Accepted 2013-NOV-28 by PPORRAS Plos One 2013 Only protein-protein interactions imex curation pdia1_human Protein disulfide-isomerase P4HB PDI PDIA1 PO4DB Prolyl 4-hydroxylase subunit beta Cellular thyroid hormone-binding protein p55 ERBA2L protein protein human Homo sapiens Human MLRRALLCLAVAALVRADAPEEEDHVLVLRKSNFAEALAAHKYLLVEFYAPWCGHCKALAPEYAKAAGKLKAEGSEIRLAKVDATEESDLAQQYGVRGYPTIKFFRNGDTASPKEYTAGREADDIVNWLKKRTGPAATTLPDGAAAESLVESSEVAVIGFFKDVESDSAKQFLQAAEAIDDIPFGITSNSDVFSKYQLDKDGVVLFKKFDEGRNNFEGEVTKENLLDFIKHNQLPLVIEFTEQTAPKIFGGEIKTHILLFLPKSVSDYDGKLSNFKTAAESFKGKILFIFIDSDHTDNQRILEFFGLKKEECPAVRLITLEEEMTKYKPESEELTAERITEFCHRFLEGKIKPHLMSQELPEDWDKQPVKVLVGKNFEDVAFDEKKNVFVEFYAPWCGHCKQLAPIWDKLGETYKDHENIVIAKMDSTANEVEAVKVHSFPTLKFFPASADRTVIDYNGERTLDGFKKFLESGGQDGAGDDDDLEDLEEAEEPDMEEDDDQKAVKDEL DIP protein P07237 original sequence version: 198 906CE6D9900B8FCE tau_human Microtubule-associated protein tau MAPT MTBT1 TAU Neurofibrillary tangle protein Paired helical filament-tau MAPTL protein protein human Homo sapiens Human MAEPRQEFEVMEDHAGTYGLGDRKDQGGYTMHQDQEGDTDAGLKESPLQTPTEDGSEEPGSETSDAKSTPTAEDVTAPLVDEGAPGKQAAAQPHTEIPEGTTAEEAGIGDTPSLEDEAAGHVTQEPESGKVVQEGFLREPGPPGLSHQLMSGMPGAPLLPEGPREATRQPSGTGPEDTEGGRHAPELLKHQLLGDLHQEGPPLKGAGGKERPGSKEEVDEDRDVDESSPQDSPPSKASPAQDGRPPQTAAREATSIPGFPAEGAIPLPVDFLSKVSTEIPASEPDGPSVGRAKGQDAPLEFTFHVEITPNVQKEQAHSEEHLGRAAFPGAPGEGPEARGPSLGEDTKEADLPEPSEKQPAAAPRGKPVSRVPQLKARMVSKSKDGTGSDDKKAKTSTRSSAKTLKNRPCLSPKHPTPGSSDPLIQPSSPAVCPEPPSSPKYVSSVTSRTGSSGAKEMKLKGADGKTKIATPRGAAPPGQKGQANATRIPAKTPPAPKTPPSSGEPPKSGDRSGYSSPGSPGTPGSRSRTPSLPTPPTREPKKVAVVRTPPKSPSSAKSRLQTAPVPMPDLKNVKSKIGSTENLKHQPGGGKVQIINKKLDLSNVQSKCGSKDNIKHVPGGGSVQIVYKPVDLSKVTSKCGSLGNIHHKPGGGQVEVKSEKLDFKDRVQSKIGSLDNITHVPGGGNKKIETHKLTFRENAKAKTDHGAEIVYKSPVVSGDTSPRHLSNVSSTGSIDMVDSPQLATLADEVSASLAKQGL DIP protein P10636 original sequence version: 125 DIP protein P10636 original sequence version: 210 D46C66CDBCD196E8 p10636-8 Microtubule-associated protein tau Tau-4 MAPT MAPTL MTBT1 TAU Neurofibrillary tangle protein Paired helical filament-tau 2N4R protein protein human Homo sapiens Human MAEPRQEFEVMEDHAGTYGLGDRKDQGGYTMHQDQEGDTDAGLKESPLQTPTEDGSEEPGSETSDAKSTPTAEDVTAPLVDEGAPGKQAAAQPHTEIPEGTTAEEAGIGDTPSLEDEAAGHVTQARMVSKSKDGTGSDDKKAKGADGKTKIATPRGAAPPGQKGQANATRIPAKTPPAPKTPPSSGEPPKSGDRSGYSSPGSPGTPGSRSRTPSLPTPPTREPKKVAVVRTPPKSPSSAKSRLQTAPVPMPDLKNVKSKIGSTENLKHQPGGGKVQIINKKLDLSNVQSKCGSKDNIKHVPGGGSVQIVYKPVDLSKVTSKCGSLGNIHHKPGGGQVEVKSEKLDFKDRVQSKIGSLDNITHVPGGGNKKIETHKLTFRENAKAKTDHGAEIVYKSPVVSGDTSPRHLSNVSSTGSIDMVDSPQLATLADEVSASLAKQGL DIP protein P10636-8 original sequence version: 206 DIP protein P10636-8 original sequence version: 203 DIP protein P10636-8 original sequence version: 166 DIP protein P10636-8 original sequence version: 218 835A8706D847A8CC tht Thioflavin T small molecule small molecule chemical synthesis Chemical synthesis (Chemical synthesis) heparin Heparin small molecule small molecule chemical synthesis Chemical synthesis (Chemical synthesis) p4hb-mapt 6 8 unspecified role unspecified role prey prey 7 unspecified role unspecified role bait bait region ha tag ha tag YPYDVPDYA epitope tag YPYDVPDYA epitope tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined physical association physical association Fig 1 p4hb-mapt-1 4 7 unspecified role unspecified role neutral component neutral component region ha tag ha tag YPYDVPDYA epitope tag YPYDVPDYA epitope tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined 8 unspecified role unspecified role neutral component neutral component colocalization colocalization Fig 2 mapt-p4hb 2 7 unspecified role unspecified role neutral component neutral component a_domain required to bind necessary binding region required to bind range range range range n_terminus his tag his tag Hexa-His-tag 6-His-tag Histidine-tag Hexa-His-tag Histidine-tag 6-His-tag n-term range n-terminal range n-term range n-term range n-terminal range n-term range ecoli Escherichia coli (strain K12) 9 unspecified role unspecified role neutral component neutral component region sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain ecoli Escherichia coli (strain K12) direct interaction direct interaction Fig 3, Table 1. Supp fig 2/3. One full-length human PDI bound to one Tau244–372 molecule with a dissociation constant of 3.46 uM at 25.0°C and 4.83 uM at 37.0°C. The binding affinity of the "a-domain" of human PDI to Tau244–372 monomer was significantly higher than that of full-length human PDI, with a dissociation constant of 0.48 uM at 25.0°C and 1.34 uM at 37.0°C. heparin-mapt-1 1 11 stimulator stimulator unspecified role unspecified role pig Sus scrofa (Pig) Pig 9 unspecified role unspecified role neutral component neutral component region sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain ecoli Escherichia coli (strain K12) 7 inhibitor inhibitor unspecified role unspecified role a_domain required to bind necessary binding region required to bind range range range range n_terminus his tag his tag Hexa-His-tag 6-His-tag Histidine-tag Hexa-His-tag Histidine-tag 6-His-tag n-term range n-terminal range n-term range n-term range n-terminal range n-term range ecoli Escherichia coli (strain K12) 9 unspecified role unspecified role neutral component neutral component region sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain ecoli Escherichia coli (strain K12) 10 unspecified role unspecified role unspecified role unspecified role chemical synthesis Chemical synthesis (Chemical synthesis) 29 34 physical association physical association Fig 4/8, Supp fig 4 The addition of seeds significantly reduced the lag time of Tau244–372 fibrillization. The inhibitory effect of human PDI on the nucleation step of Tau fibrillization under crowded physiological conditions (in Ficoll) is much stronger than that in dilute solutions. Full-length human PDI added after 190 seconds did not inhibit fibril formation of Tau244–372 under reducing conditions. heparin-mapt-2 3 11 stimulator stimulator unspecified role unspecified role pig Sus scrofa (Pig) Pig 7 inhibitor inhibitor neutral component neutral component a_domain required to bind necessary binding region required to bind range range range range n_terminus his tag his tag Hexa-His-tag 6-His-tag Histidine-tag Hexa-His-tag Histidine-tag 6-His-tag n-term range n-terminal range n-term range n-term range n-terminal range n-term range ecoli Escherichia coli (strain K12) 9 unspecified role unspecified role neutral component neutral component region sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain ecoli Escherichia coli (strain K12) 9 unspecified role unspecified role neutral component neutral component region sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain ecoli Escherichia coli (strain K12) 44 42 physical association physical association Fig 5, Supp fig 5. The addition of full-length human PDI or the a-domain resulted in a lag time of Tau244–372 fibrillization remarkably longer than that in the absence of PDI. The a-domain of human PDI inhibited Tau244–372 fibrillization more strongly than full-length human PDI. heparin-mapt-3 5 9 unspecified role unspecified role neutral component neutral component region sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain ecoli Escherichia coli (strain K12) 11 stimulator stimulator unspecified role unspecified role pig Sus scrofa (Pig) Pig 9 unspecified role unspecified role neutral component neutral component region sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain ecoli Escherichia coli (strain K12) 7 inhibitor inhibitor neutral component neutral component a_domain required to bind necessary binding region required to bind range range range range n_terminus his tag his tag Hexa-His-tag 6-His-tag Histidine-tag Hexa-His-tag Histidine-tag 6-His-tag n-term range n-terminal range n-term range n-term range n-terminal range n-term range ecoli Escherichia coli (strain K12) 47 50 physical association physical association Fig 6/7 The addition of full-length human PDI inhibited Tau244–372 fibrillization at physiological pH, and the a-domain of human PDI inhibited Tau244–372 fibrillization more strongly than full-length human PDI.