Inhibition of α-Synuclein Aggregation by the Interaction Between Protein Disulfide Isomerase and α-Synuclein
Abnormally misfolded and aggregated α-synuclein (αsyn) is the hallmark of Parkinson's disease (PD). Molecular chaperone protein disulfide isomerase (PDI) has been shown to interact with αsyn and inhibit its aggregation in vitro, but the mechanism for the recognition of αsyn by PDI is not yet cl...
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| Format: | Article |
| Language: | zho |
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Science Press
2022-12-01
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| Series: | Chinese Journal of Magnetic Resonance |
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| Online Access: | http://121.43.60.238/bpxzz/article/2022/1000-4556/20220401.shtml |
| _version_ | 1827973522406768640 |
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| author | PEI Yun-shan1,2, ZHANG Cai1,2, LIU Xiao-li1, CHENG Kai1, ZHANG Ze-ting,1, LI Cong-gang1 |
| author_facet | PEI Yun-shan1,2, ZHANG Cai1,2, LIU Xiao-li1, CHENG Kai1, ZHANG Ze-ting,1, LI Cong-gang1 |
| author_sort | PEI Yun-shan1,2, ZHANG Cai1,2, LIU Xiao-li1, CHENG Kai1, ZHANG Ze-ting,1, LI Cong-gang1 |
| collection | DOAJ |
| description | Abnormally misfolded and aggregated α-synuclein (αsyn) is the hallmark of Parkinson's disease (PD). Molecular chaperone protein disulfide isomerase (PDI) has been shown to interact with αsyn and inhibit its aggregation in vitro, but the mechanism for the recognition of αsyn by PDI is not yet clear. Herein, we used nuclear magnetic resonance (NMR) spectroscopy to identify that human PDI b'xa' bound with the N-terminal domain of αsyn, and thioflavin T (ThT) fluorescence assay revealed that b'xa' domain of PDI significantly inhibited αsyn aggregation. Furthermore, by using NMR titration, we observed that PDI bound to αsyn mainly through its hydrophobic cavity of the b' domain. Based on these findings, a docking model of PDI binding with αsyn was established and a possible mechanism of how PDI inhibits αsyn aggregation was proposed. Our work provides experimental evidences for understanding the inhibitory role of PDI in αsyn aggregation. |
| first_indexed | 2024-04-09T19:40:42Z |
| format | Article |
| id | doaj.art-1c0da6949db94c86891208586180661b |
| institution | Directory Open Access Journal |
| issn | 1000-4556 |
| language | zho |
| last_indexed | 2024-04-09T19:40:42Z |
| publishDate | 2022-12-01 |
| publisher | Science Press |
| record_format | Article |
| series | Chinese Journal of Magnetic Resonance |
| spelling | doaj.art-1c0da6949db94c86891208586180661b2023-04-04T07:55:53ZzhoScience PressChinese Journal of Magnetic Resonance1000-45562022-12-01390438139210.11938/cjmr20222974Inhibition of α-Synuclein Aggregation by the Interaction Between Protein Disulfide Isomerase and α-SynucleinPEI Yun-shan1,2, ZHANG Cai1,2, LIU Xiao-li1, CHENG Kai1, ZHANG Ze-ting,1, LI Cong-gang101. CAS Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences, Wuhan 430071, China 2. University of Chinese Academy of Sciences, Beijing 100049, ChinaAbnormally misfolded and aggregated α-synuclein (αsyn) is the hallmark of Parkinson's disease (PD). Molecular chaperone protein disulfide isomerase (PDI) has been shown to interact with αsyn and inhibit its aggregation in vitro, but the mechanism for the recognition of αsyn by PDI is not yet clear. Herein, we used nuclear magnetic resonance (NMR) spectroscopy to identify that human PDI b'xa' bound with the N-terminal domain of αsyn, and thioflavin T (ThT) fluorescence assay revealed that b'xa' domain of PDI significantly inhibited αsyn aggregation. Furthermore, by using NMR titration, we observed that PDI bound to αsyn mainly through its hydrophobic cavity of the b' domain. Based on these findings, a docking model of PDI binding with αsyn was established and a possible mechanism of how PDI inhibits αsyn aggregation was proposed. Our work provides experimental evidences for understanding the inhibitory role of PDI in αsyn aggregation.http://121.43.60.238/bpxzz/article/2022/1000-4556/20220401.shtmlnuclear magnetic resonance (nmr) ; α-synuclein (αsyn) ; protein disulfide isomerase ; interaction ; fibrillation； |
| spellingShingle | PEI Yun-shan1,2, ZHANG Cai1,2, LIU Xiao-li1, CHENG Kai1, ZHANG Ze-ting,1, LI Cong-gang1 Inhibition of α-Synuclein Aggregation by the Interaction Between Protein Disulfide Isomerase and α-Synuclein Chinese Journal of Magnetic Resonance nuclear magnetic resonance (nmr) ; α-synuclein (αsyn) ; protein disulfide isomerase ; interaction ; fibrillation； |
| title | Inhibition of α-Synuclein Aggregation by the Interaction Between Protein Disulfide Isomerase and α-Synuclein |
| title_full | Inhibition of α-Synuclein Aggregation by the Interaction Between Protein Disulfide Isomerase and α-Synuclein |
| title_fullStr | Inhibition of α-Synuclein Aggregation by the Interaction Between Protein Disulfide Isomerase and α-Synuclein |
| title_full_unstemmed | Inhibition of α-Synuclein Aggregation by the Interaction Between Protein Disulfide Isomerase and α-Synuclein |
| title_short | Inhibition of α-Synuclein Aggregation by the Interaction Between Protein Disulfide Isomerase and α-Synuclein |
| title_sort | inhibition of α synuclein aggregation by the interaction between protein disulfide isomerase and α synuclein |
| topic | nuclear magnetic resonance (nmr) ; α-synuclein (αsyn) ; protein disulfide isomerase ; interaction ; fibrillation； |
| url | http://121.43.60.238/bpxzz/article/2022/1000-4556/20220401.shtml |
| work_keys_str_mv | AT peiyunshan12zhangcai12liuxiaoli1chengkai1zhangzeting1liconggang1 inhibitionofasynucleinaggregationbytheinteractionbetweenproteindisulfideisomeraseandasynuclein |