Abundant neuroprotective chaperone Lipocalin-type prostaglandin D synthase (L-PGDS) disassembles the Amyloid-β fbrils
Misfolding of Amyloid β (Aβ) peptides leads to the formation of extracellular amyloid plaques. Molecular chaperones can facilitate the refolding or degradation of such misfolded proteins. Here, for the first time, we report the unique ability of Lipocalin-type Prostaglandin D synthase (L-PGDS) prote...
| Main Authors: | , , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
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2020
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| Online Access: | https://hdl.handle.net/10356/142559 |
| _version_ | 1811677604361535488 |
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| author | Kannaian, Bhuvaneswari Sharma, Bhargy Phillips, Margaret Chowdhury, Anup Manimekalai, Malathy Sony Subramanian Adav, Sunil Shankar Ng, Justin Tze Yang Kumar, Ambrish Lim, Sierin Mu, Yuguang Sze, Siu Kwan Grüber, Gerhard Pervushin, Konstantin |
| author2 | School of Chemical and Biomedical Engineering |
| author_facet | School of Chemical and Biomedical Engineering Kannaian, Bhuvaneswari Sharma, Bhargy Phillips, Margaret Chowdhury, Anup Manimekalai, Malathy Sony Subramanian Adav, Sunil Shankar Ng, Justin Tze Yang Kumar, Ambrish Lim, Sierin Mu, Yuguang Sze, Siu Kwan Grüber, Gerhard Pervushin, Konstantin |
| author_sort | Kannaian, Bhuvaneswari |
| collection | NTU |
| description | Misfolding of Amyloid β (Aβ) peptides leads to the formation of extracellular amyloid plaques. Molecular chaperones can facilitate the refolding or degradation of such misfolded proteins. Here, for the first time, we report the unique ability of Lipocalin-type Prostaglandin D synthase (L-PGDS) protein to act as a disaggregase on the pre-formed fibrils of Aβ(1–40), abbreviated as Aβ40, and Aβ(25–35) peptides, in addition to inhibiting the aggregation of Aβ monomers. Furthermore, our proteomics results indicate that L-PGDS can facilitate extraction of several other proteins from the insoluble aggregates extracted from the brain of an Alzheimer’s disease patient. In this study, we have established the mode of binding of L-PGDS with monomeric and fibrillar Aβ using Nuclear Magnetic Resonance (NMR) Spectroscopy, Small Angle X-ray Scattering (SAXS), and Transmission Electron Microscopy (TEM). Our results confirm a direct interaction between L-PGDS and monomeric Aβ40 and Aβ(25–35), thereby inhibiting their spontaneous aggregation. The monomeric unstructured Aβ40 binds to L-PGDS via its C-terminus, while the N-terminus remains free which is observed as a new domain in the L-PGDS-Aβ40 complex model. |
| first_indexed | 2024-10-01T02:40:00Z |
| format | Journal Article |
| id | ntu-10356/142559 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T02:40:00Z |
| publishDate | 2020 |
| record_format | dspace |
| spelling | ntu-10356/1425592023-02-28T17:07:49Z Abundant neuroprotective chaperone Lipocalin-type prostaglandin D synthase (L-PGDS) disassembles the Amyloid-β fbrils Kannaian, Bhuvaneswari Sharma, Bhargy Phillips, Margaret Chowdhury, Anup Manimekalai, Malathy Sony Subramanian Adav, Sunil Shankar Ng, Justin Tze Yang Kumar, Ambrish Lim, Sierin Mu, Yuguang Sze, Siu Kwan Grüber, Gerhard Pervushin, Konstantin School of Chemical and Biomedical Engineering School of Biological Sciences Lee Kong Chian School of Medicine (LKCMedicine) Singapore Phenome Centre Science::Biological sciences Chaperones Structural Biology Misfolding of Amyloid β (Aβ) peptides leads to the formation of extracellular amyloid plaques. Molecular chaperones can facilitate the refolding or degradation of such misfolded proteins. Here, for the first time, we report the unique ability of Lipocalin-type Prostaglandin D synthase (L-PGDS) protein to act as a disaggregase on the pre-formed fibrils of Aβ(1–40), abbreviated as Aβ40, and Aβ(25–35) peptides, in addition to inhibiting the aggregation of Aβ monomers. Furthermore, our proteomics results indicate that L-PGDS can facilitate extraction of several other proteins from the insoluble aggregates extracted from the brain of an Alzheimer’s disease patient. In this study, we have established the mode of binding of L-PGDS with monomeric and fibrillar Aβ using Nuclear Magnetic Resonance (NMR) Spectroscopy, Small Angle X-ray Scattering (SAXS), and Transmission Electron Microscopy (TEM). Our results confirm a direct interaction between L-PGDS and monomeric Aβ40 and Aβ(25–35), thereby inhibiting their spontaneous aggregation. The monomeric unstructured Aβ40 binds to L-PGDS via its C-terminus, while the N-terminus remains free which is observed as a new domain in the L-PGDS-Aβ40 complex model. MOE (Min. of Education, S’pore) Published version 2020-06-24T06:07:41Z 2020-06-24T06:07:41Z 2019 Journal Article Kannaian, B., Sharma, B., Phillips, M., Chowdhury, A., Manimekalai, M. S. S., Adav, S. S., . . . Pervushin, K. (2019). Abundant neuroprotective chaperone Lipocalin-type prostaglandin D synthase (L-PGDS) disassembles the Amyloid-β fbrils. Scientific Reports, 9(1), 12579-. doi:10.1038/s41598-019-48819-5 2045-2322 https://hdl.handle.net/10356/142559 10.1038/s41598-019-48819-5 31467325 2-s2.0-85071628821 1 9 en Scientific Reports © 2019 The Author(s). Published by Nature Publishing Group. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Te images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. application/pdf |
| spellingShingle | Science::Biological sciences Chaperones Structural Biology Kannaian, Bhuvaneswari Sharma, Bhargy Phillips, Margaret Chowdhury, Anup Manimekalai, Malathy Sony Subramanian Adav, Sunil Shankar Ng, Justin Tze Yang Kumar, Ambrish Lim, Sierin Mu, Yuguang Sze, Siu Kwan Grüber, Gerhard Pervushin, Konstantin Abundant neuroprotective chaperone Lipocalin-type prostaglandin D synthase (L-PGDS) disassembles the Amyloid-β fbrils |
| title | Abundant neuroprotective chaperone Lipocalin-type prostaglandin D synthase (L-PGDS) disassembles the Amyloid-β fbrils |
| title_full | Abundant neuroprotective chaperone Lipocalin-type prostaglandin D synthase (L-PGDS) disassembles the Amyloid-β fbrils |
| title_fullStr | Abundant neuroprotective chaperone Lipocalin-type prostaglandin D synthase (L-PGDS) disassembles the Amyloid-β fbrils |
| title_full_unstemmed | Abundant neuroprotective chaperone Lipocalin-type prostaglandin D synthase (L-PGDS) disassembles the Amyloid-β fbrils |
| title_short | Abundant neuroprotective chaperone Lipocalin-type prostaglandin D synthase (L-PGDS) disassembles the Amyloid-β fbrils |
| title_sort | abundant neuroprotective chaperone lipocalin type prostaglandin d synthase l pgds disassembles the amyloid β fbrils |
| topic | Science::Biological sciences Chaperones Structural Biology |
| url | https://hdl.handle.net/10356/142559 |
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