Interaction of the molecular chaperone alpha B-crystallin with alpha-synuclein: Effects on amyloid fibril formation and chaperone activity
α-Synuclein is a pre-synaptic protein, the function of which is not completely understood, but its pathological form is involved in neurodegenerative diseases. In vitro, α-synuclein spontaneously forms amyloid fibrils. Here, we report that αB-crystallin, a molecular chaperone found in Lewy bodies th...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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2004
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| _version_ | 1826256482858958848 |
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| author | Rekas, A Adda, C Aquilina, J Barnham, K Sunde, M Galatis, D Williamson, N Masters, C Anders, R Robinson, C Cappai, R Carver, J |
| author_facet | Rekas, A Adda, C Aquilina, J Barnham, K Sunde, M Galatis, D Williamson, N Masters, C Anders, R Robinson, C Cappai, R Carver, J |
| author_sort | Rekas, A |
| collection | OXFORD |
| description | α-Synuclein is a pre-synaptic protein, the function of which is not completely understood, but its pathological form is involved in neurodegenerative diseases. In vitro, α-synuclein spontaneously forms amyloid fibrils. Here, we report that αB-crystallin, a molecular chaperone found in Lewy bodies that are characteristic of Parkinson's disease (PD), is a potent in vitro inhibitor of α-synuclein fibrillization, both of wild-type and the two mutant forms (A30P and A53T) that cause familial, early onset PD. In doing so, large irregular aggregates of α-synuclein and αB-crystallin are formed implying that αB-crystallin redirects α-synuclein from a fibril-formation pathway towards an amorphous aggregation pathway, thus reducing the amount of physiologically stable amyloid deposits in favor of easily degradable amorphous aggregates. α-Synuclein acts as a molecular chaperone to prevent the stress-induced, amorphous aggregation of target proteins. Compared to wild-type α-synuclein, both mutant forms have decreased chaperone activity in vitro against the aggregation of reduced insulin at 37°C and the thermally induced aggregation of βL-crystallin at 60°C. Wild-type α-synuclein abrogates the chaperone activity of αB-crystallin to prevent the precipitation of reduced insulin. Interaction between these two chaperones and formation of a complex are also indicated by NMR spectroscopy, size-exclusion chromatography and mass spectrometry. In summary, α-synuclein and αB-crystallin interact readily with each other and affect each other's properties, in particular α-synuclein fibril formation and αB-crystallin chaperone action. © 2004 Elsevier Ltd. All rights reserved. |
| first_indexed | 2024-03-06T18:02:56Z |
| format | Journal article |
| id | oxford-uuid:006e747e-f609-4eeb-9f29-cf0f1963381f |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T18:02:56Z |
| publishDate | 2004 |
| record_format | dspace |
| spelling | oxford-uuid:006e747e-f609-4eeb-9f29-cf0f1963381f2022-03-26T08:29:32ZInteraction of the molecular chaperone alpha B-crystallin with alpha-synuclein: Effects on amyloid fibril formation and chaperone activityJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:006e747e-f609-4eeb-9f29-cf0f1963381fEnglishSymplectic Elements at Oxford2004Rekas, AAdda, CAquilina, JBarnham, KSunde, MGalatis, DWilliamson, NMasters, CAnders, RRobinson, CCappai, RCarver, Jα-Synuclein is a pre-synaptic protein, the function of which is not completely understood, but its pathological form is involved in neurodegenerative diseases. In vitro, α-synuclein spontaneously forms amyloid fibrils. Here, we report that αB-crystallin, a molecular chaperone found in Lewy bodies that are characteristic of Parkinson's disease (PD), is a potent in vitro inhibitor of α-synuclein fibrillization, both of wild-type and the two mutant forms (A30P and A53T) that cause familial, early onset PD. In doing so, large irregular aggregates of α-synuclein and αB-crystallin are formed implying that αB-crystallin redirects α-synuclein from a fibril-formation pathway towards an amorphous aggregation pathway, thus reducing the amount of physiologically stable amyloid deposits in favor of easily degradable amorphous aggregates. α-Synuclein acts as a molecular chaperone to prevent the stress-induced, amorphous aggregation of target proteins. Compared to wild-type α-synuclein, both mutant forms have decreased chaperone activity in vitro against the aggregation of reduced insulin at 37°C and the thermally induced aggregation of βL-crystallin at 60°C. Wild-type α-synuclein abrogates the chaperone activity of αB-crystallin to prevent the precipitation of reduced insulin. Interaction between these two chaperones and formation of a complex are also indicated by NMR spectroscopy, size-exclusion chromatography and mass spectrometry. In summary, α-synuclein and αB-crystallin interact readily with each other and affect each other's properties, in particular α-synuclein fibril formation and αB-crystallin chaperone action. © 2004 Elsevier Ltd. All rights reserved. |
| spellingShingle | Rekas, A Adda, C Aquilina, J Barnham, K Sunde, M Galatis, D Williamson, N Masters, C Anders, R Robinson, C Cappai, R Carver, J Interaction of the molecular chaperone alpha B-crystallin with alpha-synuclein: Effects on amyloid fibril formation and chaperone activity |
| title | Interaction of the molecular chaperone alpha B-crystallin with alpha-synuclein: Effects on amyloid fibril formation and chaperone activity |
| title_full | Interaction of the molecular chaperone alpha B-crystallin with alpha-synuclein: Effects on amyloid fibril formation and chaperone activity |
| title_fullStr | Interaction of the molecular chaperone alpha B-crystallin with alpha-synuclein: Effects on amyloid fibril formation and chaperone activity |
| title_full_unstemmed | Interaction of the molecular chaperone alpha B-crystallin with alpha-synuclein: Effects on amyloid fibril formation and chaperone activity |
| title_short | Interaction of the molecular chaperone alpha B-crystallin with alpha-synuclein: Effects on amyloid fibril formation and chaperone activity |
| title_sort | interaction of the molecular chaperone alpha b crystallin with alpha synuclein effects on amyloid fibril formation and chaperone activity |
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