Tau induces formation of α-synuclein filaments with distinct molecular conformations
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nihms-1689218.pdf
Description
Accepted version
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1.45 MB
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Checksum (MD5)
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Author(s)
Hojjatian, Alimohammad
Dasari, Anvesh KR
Sengupta, Urmi
Taylor, Dianne
Daneshparvar, Nadia
Yeganeh, Fatemeh Abbasi
Dillard, Lucas
Michael, Brian
Griffin, Robert G
Borgnia, Mario J
Date Issued
2021
Journal
Biochemical and Biophysical Research Communications
Publisher
Elsevier BV
Citation
Hojjatian, Alimohammad, Dasari, Anvesh KR, Sengupta, Urmi, Taylor, Dianne, Daneshparvar, Nadia et al. 2021. "Tau induces formation of α-synuclein filaments with distinct molecular conformations." Biochemical and Biophysical Research Communications, 554.
Version
Author's final manuscript
Abstract
Recent structural investigation of amyloid filaments extracted from human patients demonstrated that the ex vivo filaments associated with different disease phenotypes adopt diverse molecular conformations, which are different from those of in vitro amyloid filaments. A very recent cryo-EM structural study also revealed that ex vivo α-synuclein filaments extracted from multiple system atrophy patients adopt distinct molecular structures from those of in vitro α-synuclein filaments, suggesting the presence of co-factors for α-synuclein aggregation in vivo. Here, we report structural characterizations of α-synuclein filaments formed in the presence of a potential co-factor, tau, using cryo-EM and solid-state NMR. Our cryo-EM structure of the tau-promoted α-synuclein filaments reveals some similarities to one of the previously reported polymorphs of in vitro α-synuclein filaments in the core region, while illustrating distinct conformations in the N- and C-terminal regions. The structural study highlights the conformational plasticity of α-synuclein filaments and the importance of the co-factors, requiring additional structural investigation of not only more ex vivo α-synuclein filaments, but also in vitro α-synuclein filaments formed in the presence of diverse co-factors. The comparative structural analyses will help better understand molecular basis of diverse structures of α-synuclein filaments and possible relevance of each structure to the disease phenotype.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
Francis Bitter Magnet Laboratory (Massachusetts Institute of Technology)
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Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/J.BBRC.2021.03.091
