| Autor: |
Sanders HM; Department of Chemistry and Biochemistry and Bio5 Institute, University of Arizona, 1306 East University Boulevard, Tucson, Arizona 85721, United States., Kostelic MM; Department of Chemistry and Biochemistry and Bio5 Institute, University of Arizona, 1306 East University Boulevard, Tucson, Arizona 85721, United States., Zak CK; Department of Chemistry and Biochemistry and Bio5 Institute, University of Arizona, 1306 East University Boulevard, Tucson, Arizona 85721, United States., Marty MT; Department of Chemistry and Biochemistry and Bio5 Institute, University of Arizona, 1306 East University Boulevard, Tucson, Arizona 85721, United States. |
| Jazyk: |
angličtina |
| Zdroj: |
Biochemistry [Biochemistry] 2022 Jun 07; Vol. 61 (11), pp. 1014-1021. Date of Electronic Publication: 2022 May 26. |
| DOI: |
10.1021/acs.biochem.2c00160 |
| Abstrakt: |
Lipid membranes have recently been implicated in protein misfolding and disease etiology, including for α-synuclein and Parkinson's disease. However, studying the intersection of protein complex formation, membrane interactions, and bilayer disruption simultaneously is challenging. In particular, the efficacies of small molecule inhibitors for toxic protein aggregation are not well understood. Here, we used native mass spectrometry in combination with lipid nanodiscs to study α-synuclein-membrane interactions. α-Synuclein did not interact with zwitterionic 1,2-dimyristoyl- sn -glycero-3-phosphocholine lipids but interacted strongly with anionic 1,2-dimyristoyl- sn -glycero-3-phospho(1'- rac -glycerol) lipids, eventually leading to membrane disruption. Unsaturated 1-palmitoyl-2-oleoyl- sn -glycero-3-phospho(1'- rac -glycerol) (POPG) lipid nanodiscs were also prone to bilayer disruption, releasing α-synuclein:POPG complexes. Interestingly, the fibril inhibitor, (-)-epigallocatechin gallate (EGCG), prevented membrane disruption but did not prevent the incorporation of α-synuclein into nanodisc complexes. Thus, although EGCG inhibits fibrillization, it does not inhibit α-synuclein from associating with the membrane. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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