MINT MINT, Dpt of Biology, University of Rome Tor Vergata MINT http://mint.bio.uniroma2.it/mint url>http://mint.bio.uniroma2.it/mint/ https://mint.bio.uniroma2.it MINT-[0-9]+ https://mint.bio.uniroma2.it/index.php/results-interactions/?id=${ac} The Molecular INTeraction database (MINT) is a relational database designed to store interactions between biological molecules. http://mint.bio.uniroma2.it A comparative analysis of the aggregation behavior of amyloid-β peptide variants. A comparative analysis of the aggregation behavior of amyloid-β peptide variants. FEBS Lett. (0014-5793) 2012 Vandersteen A., Hubin E., Sarroukh R., De Baets G., Schymkowitz J., Rousseau F., Subramaniam V., Raussens V., Wenschuh H., Wildemann D., Broersen K. in vitro In vitro filter binding filter binding Filter overlay assay Filter overlay assay peptide synthesis peptide synthesis Vandersteen A., Hubin E., Sarroukh R., De Baets G., Schymkowitz J., Rousseau F., Subramaniam V., Raussens V., Wenschuh H., Wildemann D., Broersen K. FEBS Lett. (0014-5793) 2012 A comparative analysis of the aggregation behavior of amyloid-β peptide variants. A comparative analysis of the aggregation behavior of amyloid-β peptide variants. FEBS Lett. (0014-5793) 2012 Vandersteen A., Hubin E., Sarroukh R., De Baets G., Schymkowitz J., Rousseau F., Subramaniam V., Raussens V., Wenschuh H., Wildemann D., Broersen K. in vitro In vitro tem transmission electron microscopy tem peptide synthesis peptide synthesis Vandersteen A., Hubin E., Sarroukh R., De Baets G., Schymkowitz J., Rousseau F., Subramaniam V., Raussens V., Wenschuh H., Wildemann D., Broersen K. FEBS Lett. (0014-5793) 2012 A comparative analysis of the aggregation behavior of amyloid-β peptide variants. A comparative analysis of the aggregation behavior of amyloid-β peptide variants. FEBS Lett. (0014-5793) 2012 Vandersteen A., Hubin E., Sarroukh R., De Baets G., Schymkowitz J., Rousseau F., Subramaniam V., Raussens V., Wenschuh H., Wildemann D., Broersen K. in vitro In vitro fluorescence fluorescence technology fluorescence peptide synthesis peptide synthesis Vandersteen A., Hubin E., Sarroukh R., De Baets G., Schymkowitz J., Rousseau F., Subramaniam V., Raussens V., Wenschuh H., Wildemann D., Broersen K. FEBS Lett. (0014-5793) 2012 a4_human Amyloid-beta precursor protein APP A4 AD1 Alzheimer disease amyloid protein ABPP PreA4 Cerebral vascular amyloid peptide Protease nexin-II APPI Amyloid precursor protein Amyloid-beta A4 protein Alzheimer disease amyloid A4 protein homolog Amyloid-beta (A4) precursor protein protein protein human Homo sapiens Human MLPGLALLLLAAWTARALEVPTDGNAGLLAEPQIAMFCGRLNMHMNVQNGKWDSDPSGTKTCIDTKEGILQYCQEVYPELQITNVVEANQPVTIQNWCKRGRKQCKTHPHFVIPYRCLVGEFVSDALLVPDKCKFLHQERMDVCETHLHWHTVAKETCSEKSTNLHDYGMLLPCGIDKFRGVEFVCCPLAEESDNVDSADAEEDDSDVWWGGADTDYADGSEDKVVEVAEEEEVAEVEEEEADDDEDDEDGDEVEEEAEEPYEEATERTTSIATTTTTTTESVEEVVREVCSEQAETGPCRAMISRWYFDVTEGKCAPFFYGGCGGNRNNFDTEEYCMAVCGSAMSQSLLKTTQEPLARDPVKLPTTAASTPDAVDKYLETPGDENEHAHFQKAKERLEAKHRERMSQVMREWEEAERQAKNLPKADKKAVIQHFQEKVESLEQEAANERQQLVETHMARVEAMLNDRRRLALENYITALQAVPPRPRHVFNMLKKYVRAEQKDRQHTLKHFEHVRMVDPKKAAQIRSQVMTHLRVIYERMNQSLSLLYNVPAVAEEIQDEVDELLQKEQNYSDDVLANMISEPRISYGNDALMPSLTETKTTVELLPVNGEFSLDDLQPWHSFGADSVPANTENEVEPVDARPAADRGLTTRPGSGLTNIKTEEISEVKMDAEFRHDSGYEVHHQKLVFFAEDVGSNKGAIIGLMVGGVVIATVIVITLVMLKKKQYTSIHHGVVEVDAAVTPEERHLSKMQQNGYENPTYKFFEQMQN DIP protein P05067 original sequence version: 160 DIP protein P05067 original sequence version: 207 DIP protein P05067 original sequence version: 185 DIP protein P05067 original sequence version: 188 A12EE761403740F5 app-app-13 3 Amyloid beta 4 peptide synthesis peptide synthesis experimental particp experimental participant identification experimental particp unspecified role unspecified role neutral component neutral component purified purified binding site binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain Amyloid beta 4 peptide synthesis peptide synthesis experimental particp experimental participant identification experimental particp unspecified role unspecified role neutral component neutral component purified purified binding site binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain direct interaction direct interaction homomint mint Aggregation kinetics of various Aβ lengths were recorded by ThT fluorescence and two different aggregation profiles could be distinguished: slow aggregation accompanied with long nucleation times and high final fluorescence intensity were detected for Aβ1-37, Aβ1-38 and Aβ1-40, while Aβ1-42 and Aβ1-43 aggregated rapidly with almost immediate onset resulting in low final fluorescence intensity (Fig 1A,B). N- and C-terminal biotinylation of Aβ1-40 increased 1 the lag time of aggregation (Fig 2 3A) while decreasing final ThT fluorescence (Fig 3A,B), indicative of inhibited 3 aggregation, without affecting fibril morphology (Fig 3C). f1a f1bf3a f3b app-app-14 3 Amyloid beta 4 peptide synthesis peptide synthesis experimental particp experimental participant identification experimental particp unspecified role unspecified role neutral component neutral component purified purified undefined mutation mutation decreasing interaction mutation increasing mutation increasing interaction mutation increasing mutation analysis mutation analysis certain certain sequence position certain certain certain sequence position certain Wed Jul 06 16:42:42 BST 2016 Sequence change details about this feature cannot be ascertained or do not fit with the current version of the referenced protein, so they have been deleted as a result of our quality control procedures. The original label was 'mutation decreasing' Ala21Gly binding site binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain Amyloid beta 4 peptide synthesis peptide synthesis experimental particp experimental participant identification experimental particp unspecified role unspecified role neutral component neutral component purified purified binding site binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain undefined mutation mutation decreasing interaction mutation increasing mutation increasing interaction mutation increasing mutation analysis mutation analysis certain certain sequence position certain certain certain sequence position certain Wed Jul 06 16:42:44 BST 2016 Sequence change details about this feature cannot be ascertained or do not fit with the current version of the referenced protein, so they have been deleted as a result of our quality control procedures. The original label was 'mutation decreasing' Ala21Gly direct interaction direct interaction f2a f2b homomint mint Familial mutations of Aβ1-42 displayed a short nucleation phase similar to that observed for wild type Aβ1-42, but affected the rate of fibril elongation and final ThT fluorescence intensity (Fig 2A,B). The slow polymerization of the D23N mutation coincided with a very low final ThT fluorescence, while A21G and E22Q mutations of Aβ1-42 aggregated at a higher rate with an increased final ThT fluorescence intensity compared to wild type Aβ1-42. All these mutants of Ab1-42 have been tested :D7N - A21G - E22G - E22K - E22Q - D23N. app-app-15 3 Amyloid beta 4 peptide synthesis peptide synthesis experimental particp experimental participant identification experimental particp unspecified role unspecified role neutral component neutral component purified purified undefined mutation mutation decreasing interaction mutation increasing mutation increasing interaction mutation increasing mutation analysis mutation analysis certain certain sequence position certain certain certain sequence position certain Wed Jul 06 16:41:47 BST 2016 Sequence change details about this feature cannot be ascertained or do not fit with the current version of the referenced protein, so they have been deleted as a result of our quality control procedures. The original label was 'mutation decreasing' Glu22Gln binding site binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain Amyloid beta 4 peptide synthesis peptide synthesis experimental particp experimental participant identification experimental particp unspecified role unspecified role neutral component neutral component purified purified undefined mutation mutation decreasing interaction mutation increasing mutation increasing interaction mutation increasing mutation analysis mutation analysis certain certain sequence position certain certain certain sequence position certain Wed Jul 06 16:42:17 BST 2016 Sequence change details about this feature cannot be ascertained or do not fit with the current version of the referenced protein, so they have been deleted as a result of our quality control procedures. The original label was 'mutation decreasing' Glu22Gln binding site binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain direct interaction direct interaction f2a f2b homomint mint Familial mutations of Aβ1-42 displayed a short nucleation phase similar to that observed for wild type Aβ1-42, but affected the rate of fibril elongation and final ThT fluorescence intensity (Fig 2A,B). The slow polymerization of the D23N mutation coincided with a very low final ThT fluorescence, while A21G and E22Q mutations of Aβ1-42 aggregated at a higher rate with an increased final ThT fluorescence intensity compared to wild type Aβ1-42. All these mutants of Ab1-42 have been tested :D7N - A21G - E22G - E22K - E22Q - D23N. app-app-16 3 Amyloid beta p3 17-40 4 peptide synthesis peptide synthesis experimental particp experimental participant identification experimental particp unspecified role unspecified role neutral component neutral component purified purified binding site binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain Amyloid beta p3 17-40 4 peptide synthesis peptide synthesis experimental particp experimental participant identification experimental particp unspecified role unspecified role neutral component neutral component purified purified binding site binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain direct interaction direct interaction homomint mint f4a f4b Both N-terminally truncated forms of Aβ1-40 and Aβ1-42, p317-40 and p317-42 respectively, were characterized by rapid onset of aggregation compared to their corresponding full-length forms with decreased final ThT fluorescence intensity (Fig 4A,B). app-app-17 3 Amyloid beta 4 peptide synthesis peptide synthesis experimental particp experimental participant identification experimental particp unspecified role unspecified role neutral component neutral component purified purified P05067:p.Asp23Asn mutation decreasing interaction mutation decreasing mutation decreasing interaction hotspot hotspot mutation decreasing mutation analysis mutation analysis certain certain sequence position certain certain certain sequence position certain D N Tue Jul 12 10:20:30 BST 2016 This feature has been corrected as a result of our quality control procedures. The original label was 'mutation decreasing' Wed May 02 20:23:32 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'asp23asn' Tue Jun 30 16:05:48 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Asp23Asn' binding site binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain Amyloid beta 4 peptide synthesis peptide synthesis experimental particp experimental participant identification experimental particp unspecified role unspecified role neutral component neutral component purified purified P05067:p.Asp23Asn mutation decreasing interaction mutation decreasing mutation decreasing interaction hotspot hotspot mutation decreasing mutation analysis mutation analysis certain certain sequence position certain certain certain sequence position certain D N Tue Jul 12 10:57:08 BST 2016 This feature has been corrected as a result of our quality control procedures. The original label was 'mutation decreasing' Wed May 02 17:37:09 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'asp23asn' Tue Jun 30 17:05:29 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Asp23Asn' binding site binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain direct interaction direct interaction homomint mint Familial mutations of Aβ1-42 displayed a short nucleation phase similar to that 14 observed for wild type Aβ1-42, but affected the rate of fibril elongation and final ThT 15 fluorescence intensity (Fig 2A,B). The slow polymerization of the D23N mutation 16 coincided with a very low final ThT fluorescence, while A21G and E22Q mutations 17 of Aβ1-42 aggregated at a higher rate with an increased final ThT fluorescence 18 intensity compared to wild type Aβ1-42. f2a f2b All these mutants of Ab1-42 have been tested :D7N - A21G - E22G - E22K - E22Q - D23N. app-app-18 2 Amyloid beta 4 peptide synthesis peptide synthesis experimental particp experimental participant identification experimental particp unspecified role unspecified role neutral component neutral component purified purified binding site binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain Amyloid beta 4 peptide synthesis peptide synthesis experimental particp experimental participant identification experimental particp unspecified role unspecified role neutral component neutral component purified purified binding site binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain direct interaction direct interaction homomint mint Visualization of fibrils by TEM indeed revealed morphologically distinct aggregates, showing extended negatively-stained fibrils for Aβ1-37, Aβ1-38 and Aβ1-40, and heavily intertwined networks for Aβ1-42 and Aβ1-43 (Fig 1C). All mutants of Aβ1-42 displayed a β-sheet enriched conformation (Fig 2E, Table 1) and eventually formed similar dense fibrillar networks (Fig 2C). f1c f2c f3c app-app-19 2 Amyloid beta p3 17-40 4 peptide synthesis peptide synthesis experimental particp experimental participant identification experimental particp unspecified role unspecified role neutral component neutral component purified purified binding site binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain Amyloid beta p3 17-40 4 peptide synthesis peptide synthesis experimental particp experimental participant identification experimental particp unspecified role unspecified role neutral component neutral component purified purified binding site binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain direct interaction direct interaction f4c homomint mint From a morphological perspective, visualization by TEM revealed short fibrillar fragments for p317-40 dissimilar from the long extended networks observed for full-length Aβ1-40 (Fig 4C). Truncation of Aβ1-42 to p317-42 only slightly affected fibril morphology resulting in less curly fibrils (Fig 4C). app-app-20 1 Amyloid beta 4 peptide synthesis peptide synthesis experimental particp experimental participant identification experimental particp unspecified role unspecified role neutral component neutral component purified purified P05067:p.Asp23Asn mutation increasing mutation increasing interaction mutation increasing certain certain sequence position certain certain certain sequence position certain D N Tue Jul 12 10:08:26 BST 2016 This feature has been corrected as a result of our quality control procedures. The original label was 'mutation increasing' Wed May 02 16:33:53 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'asp23asn' Tue Jun 30 16:15:11 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Asp23Asn' binding site binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain Amyloid beta 4 peptide synthesis peptide synthesis experimental particp experimental participant identification experimental particp unspecified role unspecified role neutral component neutral component purified purified P05067:p.Asp23Asn mutation increasing interaction mutation increasing mutation increasing interaction mutation increasing mutation analysis mutation analysis certain certain sequence position certain certain certain sequence position certain D N Tue Jul 12 10:50:16 BST 2016 This feature has been corrected as a result of our quality control procedures. The original label was 'mutation increasing' Wed May 02 20:21:41 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'asp23asn' Tue Jun 30 19:42:04 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Asp23Asn' binding site binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain direct interaction direct interaction homomint mint Apart from affecting fibril properties, increasing peptide length also leads to a more pronounced oligomerization as detected through dotblotting with the oligomer-specific A11 antibody (Fig 1D). Oligomerization of the mutated Aβ1-42 peptides showed little 21 variability as seen by A11-reactivity (Fig 2D), with exception of D23N Aβ1-42 Oligomerization of biotinylated Aβ1-40, as probed by A11-reactivity, was unaffected (Fig 3D). f2d All these mutants of Ab1-42 have been tested :D7N - A21G - E22G - E22K - E22Q - D23N. app-app-21 1 Amyloid beta p3 17-40 4 peptide synthesis peptide synthesis experimental particp experimental participant identification experimental particp unspecified role unspecified role neutral component neutral component purified purified binding site binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain Amyloid beta p3 17-40 4 peptide synthesis peptide synthesis experimental particp experimental participant identification experimental particp unspecified role unspecified role neutral component neutral component purified purified binding site binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain direct interaction direct interaction f4d homomint mint Oligomerization of the truncated p3 peptides, as analyzed by A11-reactivity and the β-sheet index, was not significantly affected compared to the full-length counterparts (Fig 4D, Table 1).4C). app-app-22 1 Amyloid beta 4 peptide synthesis peptide synthesis experimental particp experimental participant identification experimental particp unspecified role unspecified role neutral component neutral component purified purified binding site binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain Amyloid beta 4 peptide synthesis peptide synthesis experimental particp experimental participant identification experimental particp unspecified role unspecified role neutral component neutral component purified purified binding site binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain direct interaction direct interaction homomint mint f1d f3d Apart from affecting fibril properties, increasing peptide length also leads to a more pronounced oligomerization as detected through dotblotting with the oligomer-specific A11 antibody (Fig 1D). Oligomerization of biotinylated Aβ1-40, as probed by A11-reactivity, was unaffected (Fig 3D).