Sequence-based identification of amyloidogenic β-hairpins reveals a prostatic acid phosphatase fragment promoting semen amyloid formation
β-Structure-rich amyloid fibrils are hallmarks of several diseases, including Alzheimer’s (AD), Parkinson’s (PD), and type 2 diabetes (T2D). While amyloid fibrils typically consist of parallel β-sheets, the anti-parallel β-hairpin is a structural motif accessible to amyloidogenic proteins in their m...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-12-01
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| Series: | Computational and Structural Biotechnology Journal |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2001037023004993 |
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| author | Laetitia F. Heid Emil Dandanell Agerschou Asuka A. Orr Tatsiana Kupreichyk Walfried Schneider Michael M. Wördehoff Melanie Schwarten Dieter Willbold Phanourios Tamamis Matthias Stoldt Wolfgang Hoyer |
| author_facet | Laetitia F. Heid Emil Dandanell Agerschou Asuka A. Orr Tatsiana Kupreichyk Walfried Schneider Michael M. Wördehoff Melanie Schwarten Dieter Willbold Phanourios Tamamis Matthias Stoldt Wolfgang Hoyer |
| author_sort | Laetitia F. Heid |
| collection | DOAJ |
| description | β-Structure-rich amyloid fibrils are hallmarks of several diseases, including Alzheimer’s (AD), Parkinson’s (PD), and type 2 diabetes (T2D). While amyloid fibrils typically consist of parallel β-sheets, the anti-parallel β-hairpin is a structural motif accessible to amyloidogenic proteins in their monomeric and oligomeric states. Here, to investigate implications of β-hairpins in amyloid formation, potential β-hairpin-forming amyloidogenic segments in the human proteome were predicted based on sequence similarity with β-hairpins previously observed in Aβ, α-synuclein, and islet amyloid polypeptide, amyloidogenic proteins associated with AD, PD, and T2D, respectively. These three β-hairpins, established upon binding to the engineered binding protein β-wrapin AS10, are characterized by proximity of two sequence segments rich in hydrophobic and aromatic amino acids, with high β-aggregation scores according to the TANGO algorithm. Using these criteria, 2505 potential β-hairpin-forming amyloidogenic segments in 2098 human proteins were identified. Characterization of a test set of eight protein segments showed that seven assembled into Thioflavin T-positive aggregates and four formed β-hairpins in complex with AS10 according to NMR. One of those is a segment of prostatic acid phosphatase (PAP) comprising amino acids 185–208. PAP is naturally cleaved into fragments, including PAP(248−286) which forms functional amyloid in semen. We find that PAP(185−208) strongly decreases the protein concentrations required for fibril formation of PAP(248−286) and of another semen amyloid peptide, SEM1(86−107), indicating that it promotes nucleation of semen amyloids. In conclusion, β-hairpin-forming amyloidogenic protein segments could be identified in the human proteome with potential roles in functional or disease-related amyloid formation. |
| first_indexed | 2024-03-08T18:29:36Z |
| format | Article |
| id | doaj.art-41def2bd09194e848abe840a29fb7370 |
| institution | Directory Open Access Journal |
| issn | 2001-0370 |
| language | English |
| last_indexed | 2024-03-08T18:29:36Z |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Computational and Structural Biotechnology Journal |
| spelling | doaj.art-41def2bd09194e848abe840a29fb73702023-12-30T04:43:21ZengElsevierComputational and Structural Biotechnology Journal2001-03702024-12-0123417430Sequence-based identification of amyloidogenic β-hairpins reveals a prostatic acid phosphatase fragment promoting semen amyloid formationLaetitia F. Heid0Emil Dandanell Agerschou1Asuka A. Orr2Tatsiana Kupreichyk3Walfried Schneider4Michael M. Wördehoff5Melanie Schwarten6Dieter Willbold7Phanourios Tamamis8Matthias Stoldt9Wolfgang Hoyer10Institut für Physikalische Biologie, Heinrich Heine University Düsseldorf, 40204 Düsseldorf, GermanyInstitut für Physikalische Biologie, Heinrich Heine University Düsseldorf, 40204 Düsseldorf, GermanyArtie McFerrin Department of Chemical Engineering, Texas A&M University, College Station, TX 77843-3122, United StatesInstitut für Physikalische Biologie, Heinrich Heine University Düsseldorf, 40204 Düsseldorf, Germany; Institute of Biological Information Processing (IBI-7) and JuStruct: Jülich Center for Structural Biology, Forschungszentrum Jülich, 52425 Jülich, GermanyInstitut für Physikalische Biologie, Heinrich Heine University Düsseldorf, 40204 Düsseldorf, GermanyInstitut für Physikalische Biologie, Heinrich Heine University Düsseldorf, 40204 Düsseldorf, GermanyInstitute of Biological Information Processing (IBI-7) and JuStruct: Jülich Center for Structural Biology, Forschungszentrum Jülich, 52425 Jülich, GermanyInstitut für Physikalische Biologie, Heinrich Heine University Düsseldorf, 40204 Düsseldorf, Germany; Institute of Biological Information Processing (IBI-7) and JuStruct: Jülich Center for Structural Biology, Forschungszentrum Jülich, 52425 Jülich, GermanyArtie McFerrin Department of Chemical Engineering, Texas A&M University, College Station, TX 77843-3122, United States; Department of Materials Science and Engineering, Texas A&M University, College Station, TX 77843-3033, United StatesInstitute of Biological Information Processing (IBI-7) and JuStruct: Jülich Center for Structural Biology, Forschungszentrum Jülich, 52425 Jülich, GermanyInstitut für Physikalische Biologie, Heinrich Heine University Düsseldorf, 40204 Düsseldorf, Germany; Institute of Biological Information Processing (IBI-7) and JuStruct: Jülich Center for Structural Biology, Forschungszentrum Jülich, 52425 Jülich, Germany; Corresponding author at: Institute of Biological Information Processing (IBI-7) and JuStruct: Jülich Center for Structural Biology, Forschungszentrum Jülich, 52425 Jülich, Germany.β-Structure-rich amyloid fibrils are hallmarks of several diseases, including Alzheimer’s (AD), Parkinson’s (PD), and type 2 diabetes (T2D). While amyloid fibrils typically consist of parallel β-sheets, the anti-parallel β-hairpin is a structural motif accessible to amyloidogenic proteins in their monomeric and oligomeric states. Here, to investigate implications of β-hairpins in amyloid formation, potential β-hairpin-forming amyloidogenic segments in the human proteome were predicted based on sequence similarity with β-hairpins previously observed in Aβ, α-synuclein, and islet amyloid polypeptide, amyloidogenic proteins associated with AD, PD, and T2D, respectively. These three β-hairpins, established upon binding to the engineered binding protein β-wrapin AS10, are characterized by proximity of two sequence segments rich in hydrophobic and aromatic amino acids, with high β-aggregation scores according to the TANGO algorithm. Using these criteria, 2505 potential β-hairpin-forming amyloidogenic segments in 2098 human proteins were identified. Characterization of a test set of eight protein segments showed that seven assembled into Thioflavin T-positive aggregates and four formed β-hairpins in complex with AS10 according to NMR. One of those is a segment of prostatic acid phosphatase (PAP) comprising amino acids 185–208. PAP is naturally cleaved into fragments, including PAP(248−286) which forms functional amyloid in semen. We find that PAP(185−208) strongly decreases the protein concentrations required for fibril formation of PAP(248−286) and of another semen amyloid peptide, SEM1(86−107), indicating that it promotes nucleation of semen amyloids. In conclusion, β-hairpin-forming amyloidogenic protein segments could be identified in the human proteome with potential roles in functional or disease-related amyloid formation.http://www.sciencedirect.com/science/article/pii/S2001037023004993Amyloidβ-hairpinProtein misfoldingProtein aggregationProteopathySemen amyloid |
| spellingShingle | Laetitia F. Heid Emil Dandanell Agerschou Asuka A. Orr Tatsiana Kupreichyk Walfried Schneider Michael M. Wördehoff Melanie Schwarten Dieter Willbold Phanourios Tamamis Matthias Stoldt Wolfgang Hoyer Sequence-based identification of amyloidogenic β-hairpins reveals a prostatic acid phosphatase fragment promoting semen amyloid formation Computational and Structural Biotechnology Journal Amyloid β-hairpin Protein misfolding Protein aggregation Proteopathy Semen amyloid |
| title | Sequence-based identification of amyloidogenic β-hairpins reveals a prostatic acid phosphatase fragment promoting semen amyloid formation |
| title_full | Sequence-based identification of amyloidogenic β-hairpins reveals a prostatic acid phosphatase fragment promoting semen amyloid formation |
| title_fullStr | Sequence-based identification of amyloidogenic β-hairpins reveals a prostatic acid phosphatase fragment promoting semen amyloid formation |
| title_full_unstemmed | Sequence-based identification of amyloidogenic β-hairpins reveals a prostatic acid phosphatase fragment promoting semen amyloid formation |
| title_short | Sequence-based identification of amyloidogenic β-hairpins reveals a prostatic acid phosphatase fragment promoting semen amyloid formation |
| title_sort | sequence based identification of amyloidogenic β hairpins reveals a prostatic acid phosphatase fragment promoting semen amyloid formation |
| topic | Amyloid β-hairpin Protein misfolding Protein aggregation Proteopathy Semen amyloid |
| url | http://www.sciencedirect.com/science/article/pii/S2001037023004993 |
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