Tau induces formation of α-synuclein filaments with distinct molecular conformations

Alimohammad Hojjatian, Anvesh K.R. Dasari, Urmi Sengupta, Dianne Taylor, Nadia Daneshparvar, Fatemeh Abbasi Yeganeh, Lucas Dillard, Brian Michael, Robert G. Griffin, Mario J. Borgnia, Rakez Kayed, Kenneth A. Taylor, Kwang Hun Lim

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)145-150
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume554
DOIs
StatePublished - May 21 2021

Keywords

  • Cryo-EM
  • Solid-state NMR
  • Tau
  • α-Synuclein

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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