Tau Interacts with the C-Terminal Region of α-Synuclein, Promoting Formation of Toxic Aggregates with Distinct Molecular Conformations

Anvesh K.R. Dasari, Rakez Kayed, Sungsool Wi, Kwang Hun Lim

Research output: Contribution to journalArticle

Abstract

An increasing body of evidence suggests that aggregation-prone proteins associated with various neurodegenerative diseases synergistically promote their mutual aggregation, leading to the co-occurrence of multiple neurodegenerative diseases in the same patient. Here we investigated teh molecular basis of synergistic interactions between the two pathological proteins, tau and α-synuclein, using various biophysical techniques including transmission electron microscopy (TEM), circular dichroism (CD), and solution and solid-state NMR. Our biophysical analyses of α-synuclein aggregation in the absence and presence of tau reveal that tau monomers promote the formation of α-synuclein oligomers and subsequently fibril formation. Solution NMR results also indicate that monomeric forms of tau selectively interact with the C-terminal region of the α-synuclein monomer, accelerating α-synuclein aggregation. In addition, a combined use of TEM and solid-state NMR spectroscopy reveals that the synergistic interactions lead to the formation of toxic α-synuclein aggregates with a distinct morphology and molecular conformation. The filamentous α-synuclein aggregates as well as α-synuclein monomers were also able to induce tau aggregation.

Original languageEnglish (US)
Pages (from-to)2814-2821
Number of pages8
JournalBiochemistry
Volume58
Issue number25
DOIs
StatePublished - Jun 25 2019

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Synucleins
Molecular Conformation
Poisons
Conformations
Agglomeration
Neurodegenerative diseases
Monomers
Transmission Electron Microscopy
Neurodegenerative Diseases
Nuclear magnetic resonance
Transmission electron microscopy
tau Proteins
Circular Dichroism
Oligomers
Nuclear magnetic resonance spectroscopy
Magnetic Resonance Spectroscopy

ASJC Scopus subject areas

  • Biochemistry

Cite this

Tau Interacts with the C-Terminal Region of α-Synuclein, Promoting Formation of Toxic Aggregates with Distinct Molecular Conformations. / Dasari, Anvesh K.R.; Kayed, Rakez; Wi, Sungsool; Lim, Kwang Hun.

In: Biochemistry, Vol. 58, No. 25, 25.06.2019, p. 2814-2821.

Research output: Contribution to journalArticle

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