Lipids and EGCG Affect α-Synuclein Association and Disruption of Nanodiscs

Henry M. Sanders, Marius M. Kostelic, Ciara K. Zak, Michael T. Marty

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1014-1021
Number of pages8
Issue number11
StatePublished - Jun 7 2022

ASJC Scopus subject areas

  • Biochemistry


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