Inhibition of peptide aggregation by means of enzymatic phosphorylation
As is the case in numerous natural processes, enzymatic phosphorylation can be used in the laboratory to influence the conformational populations of proteins. In nature, this information is used for signal transduction or energy transfer, but has also been shown to play an important role in many dis...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Beilstein-Institut
2016-11-01
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| Series: | Beilstein Journal of Organic Chemistry |
| Subjects: | |
| Online Access: | https://doi.org/10.3762/bjoc.12.240 |
| _version_ | 1818445265359601664 |
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| author | Kristin Folmert Malgorzata Broncel Hans v. Berlepsch Christopher H. Ullrich Mary-Ann Siegert Beate Koksch |
| author_facet | Kristin Folmert Malgorzata Broncel Hans v. Berlepsch Christopher H. Ullrich Mary-Ann Siegert Beate Koksch |
| author_sort | Kristin Folmert |
| collection | DOAJ |
| description | As is the case in numerous natural processes, enzymatic phosphorylation can be used in the laboratory to influence the conformational populations of proteins. In nature, this information is used for signal transduction or energy transfer, but has also been shown to play an important role in many diseases like tauopathies or diabetes. With the goal of determining the effect of phosphorylation on amyloid fibril formation, we designed a model peptide which combines structural characteristics of α-helical coiled-coils and β-sheets in one sequence. This peptide undergoes a conformational transition from soluble structures into insoluble amyloid fibrils over time and under physiological conditions and contains a recognition motif for PKA (cAMP-dependent protein kinase) that enables enzymatic phosphorylation. We have analyzed the pathway of amyloid formation and the influence of enzymatic phosphorylation on the different states along the conformational transition from random-coil to β-sheet-rich oligomers to protofilaments and on to insoluble amyloid fibrils, and we found a remarkable directing effect from β-sheet-rich structures to unfolded structures in the initial growth phase, in which small oligomers and protofilaments prevail if the peptide is phosphorylated. |
| first_indexed | 2024-12-14T19:29:05Z |
| format | Article |
| id | doaj.art-3c6372adf1f24f6baf86709258a3c23c |
| institution | Directory Open Access Journal |
| issn | 1860-5397 |
| language | English |
| last_indexed | 2024-12-14T19:29:05Z |
| publishDate | 2016-11-01 |
| publisher | Beilstein-Institut |
| record_format | Article |
| series | Beilstein Journal of Organic Chemistry |
| spelling | doaj.art-3c6372adf1f24f6baf86709258a3c23c2022-12-21T22:50:06ZengBeilstein-InstitutBeilstein Journal of Organic Chemistry1860-53972016-11-011212462247010.3762/bjoc.12.2401860-5397-12-240Inhibition of peptide aggregation by means of enzymatic phosphorylationKristin Folmert0Malgorzata Broncel1Hans v. Berlepsch2Christopher H. Ullrich3Mary-Ann Siegert4Beate Koksch5Department of Chemistry and Biochemistry, Freie Universität Berlin, Takustr. 3, 14195 Berlin, GermanyThe Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UKDepartment of Chemistry and Biochemistry, Freie Universität Berlin, Takustr. 3, 14195 Berlin, GermanyDeutsche Bahn, Umweltservice, Bahntechnikerring 74, 14774 Kirchmöser, GermanyDepartment of Organic Chemistry, Technische Universität Berlin, Strasse des 17. Juni 124, 10623 Berlin, GermanyDepartment of Chemistry and Biochemistry, Freie Universität Berlin, Takustr. 3, 14195 Berlin, GermanyAs is the case in numerous natural processes, enzymatic phosphorylation can be used in the laboratory to influence the conformational populations of proteins. In nature, this information is used for signal transduction or energy transfer, but has also been shown to play an important role in many diseases like tauopathies or diabetes. With the goal of determining the effect of phosphorylation on amyloid fibril formation, we designed a model peptide which combines structural characteristics of α-helical coiled-coils and β-sheets in one sequence. This peptide undergoes a conformational transition from soluble structures into insoluble amyloid fibrils over time and under physiological conditions and contains a recognition motif for PKA (cAMP-dependent protein kinase) that enables enzymatic phosphorylation. We have analyzed the pathway of amyloid formation and the influence of enzymatic phosphorylation on the different states along the conformational transition from random-coil to β-sheet-rich oligomers to protofilaments and on to insoluble amyloid fibrils, and we found a remarkable directing effect from β-sheet-rich structures to unfolded structures in the initial growth phase, in which small oligomers and protofilaments prevail if the peptide is phosphorylated.https://doi.org/10.3762/bjoc.12.240aggregationamyloidspeptide modelspeptide phosphorylationprotein folding |
| spellingShingle | Kristin Folmert Malgorzata Broncel Hans v. Berlepsch Christopher H. Ullrich Mary-Ann Siegert Beate Koksch Inhibition of peptide aggregation by means of enzymatic phosphorylation Beilstein Journal of Organic Chemistry aggregation amyloids peptide models peptide phosphorylation protein folding |
| title | Inhibition of peptide aggregation by means of enzymatic phosphorylation |
| title_full | Inhibition of peptide aggregation by means of enzymatic phosphorylation |
| title_fullStr | Inhibition of peptide aggregation by means of enzymatic phosphorylation |
| title_full_unstemmed | Inhibition of peptide aggregation by means of enzymatic phosphorylation |
| title_short | Inhibition of peptide aggregation by means of enzymatic phosphorylation |
| title_sort | inhibition of peptide aggregation by means of enzymatic phosphorylation |
| topic | aggregation amyloids peptide models peptide phosphorylation protein folding |
| url | https://doi.org/10.3762/bjoc.12.240 |
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