Single-Vesicle Imaging Reveals Lipid-Selective and Stepwise Membrane Disruption by Monomeric α-Synuclein | Sciact - CRIS-система Института катализа

Single-Vesicle Imaging Reveals Lipid-Selective and Stepwise Membrane Disruption by Monomeric α-Synuclein Научная публикация

Журнал

Proceedings of the National Academy of Sciences of the United States of America
ISSN: 0027-8424 , E-ISSN: 1091-6490

Вых. Данные

Год: 2020, Том: 117, Номер: 25, Страницы: 14178-14186 Страниц : 9 DOI: 10.1073/pnas.1914670117

Ключевые слова

lipid vesicle; membrane interaction; single-vesicle scattering; α-synuclein

Авторы

Hannestad Jonas K. ¹ , Rocha Sandra ² , Agnarsson Björn ¹ , Zhdanov Vladimir P. ^1,3 , Wittung-Stafshede Pernilla ² , Höök Fredrik ¹

Организации

1	Division of Nano and Biological Physics, Department of Physics, Chalmers University of Technology, Gothenburg 41296, Sweden
2	Division of Chemical Biology, Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg 41296, Sweden
3	Boreskov Institute of Catalysis, Russian Academy of Sciences, Novosibirsk 630090, Russia

Информация о финансировании (3)

1	Фонд Кнута и Элис Валленберг
2	Swedish Research Council
3	Chalmers University of Technology

The interaction of the neuronal protein α-synuclein with lipid membranes appears crucial in the context of Parkinson’s disease, but the underlying mechanistic details, including the roles of different lipids in pathogenic protein aggregation and membrane disruption, remain elusive. Here, we used single-vesicle resolution fluorescence and label-free scattering microscopy to investigate the interaction kinetics of monomeric α-synuclein with surface-tethered vesicles composed of different negatively charged lipids. Supported by a theoretical model to account for structural changes in scattering properties of surface-tethered lipid vesicles, the data demonstrate stepwise vesicle disruption and asymmetric membrane deformation upon α-synuclein binding to phosphatidylglycerol vesicles at protein concentrations down to 10 nM (∼100 proteins per vesicle). In contrast, phosphatidylserine vesicles were only marginally affected. These insights into structural consequences of α-synuclein interaction with lipid vesicles highlight the contrasting roles of different anionic lipids, which may be of mechanistic relevance for both normal protein function (e.g., synaptic vesicle binding) and dysfunction (e.g., mitochondrial membrane interaction).

Hannestad J.K. , Rocha S. , Agnarsson B. , Zhdanov V.P. , Wittung-Stafshede P. , Höök F.
Single-Vesicle Imaging Reveals Lipid-Selective and Stepwise Membrane Disruption by Monomeric α-Synuclein

Proceedings of the National Academy of Sciences of the United States of America. 2020. V.117. N25. P.14178-14186. DOI: 10.1073/pnas.1914670117 WOS Scopus РИНЦ CAPlus PMID OpenAlex

Полный текст от издателя

Поступила в редакцию:	22 авг. 2019 г.
Принята к публикации:	7 мая 2020 г.
Опубликована online:	8 июн. 2020 г.
Опубликована в печати:	23 июн. 2020 г.

Web of science:	WOS:000546772500020
Scopus:	2-s2.0-85087094711
РИНЦ:	45459155
Chemical Abstracts:	2020:1443065
PMID (PubMed):	32513706
OpenAlex:	W3033429674

БД	Цитирований
Scopus	46
Web of science	47
РИНЦ	40
OpenAlex	51