Redox State Controls Phase Separation of the Yeast Ataxin-2 Protein via Reversible Oxidation of Its Methionine-Rich Low-Complexity Domain

Masato Kato, Yu San Yang, Benjamin M. Sutter, Yun Wang, Steven L McKnight, Benjamin P Tu

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Yeast ataxin-2, also known as Pbp1, senses the activity state of mitochondria in order to regulate TORC1. A domain of Pbp1 required to adapt cells to mitochondrial activity is of low sequence complexity. The low-complexity (LC) domain of Pbp1 forms labile, cross-β polymers that facilitate phase transition of the protein into liquid-like or gel-like states. Phase transition for other LC domains is reliant upon widely distributed aromatic amino acids. In place of tyrosine or phenylalanine residues prototypically used for phase separation, Pbp1 contains 24 similarly disposed methionine residues. Here, we show that the Pbp1 methionine residues are sensitive to hydrogen peroxide (H 2 O 2 )-mediated oxidation in vitro and in living cells. Methionine oxidation melts Pbp1 liquid-like droplets in a manner reversed by methionine sulfoxide reductase enzymes. These observations explain how reversible formation of labile polymers by the Pbp1 LC domain enables the protein to function as a sensor of cellular redox state.

Original languageEnglish (US)
Pages (from-to)711-721.e8
JournalCell
Volume177
Issue number3
DOIs
StatePublished - Apr 18 2019

Fingerprint

Fungal Proteins
Phase separation
Methionine
Yeast
Oxidation-Reduction
Phase Transition
Oxidation
Polymers
Phase transitions
Aromatic Amino Acids
Mitochondria
Liquids
Phenylalanine
Hydrogen Peroxide
Tyrosine
Proteins
Yeasts
Gels
Cells
Sensors

Keywords

  • aging
  • Ataxin-2
  • cross-β polymer
  • low-complexity sequence
  • methionine
  • neurodegeneration
  • oxidative stress
  • phase separation
  • ROS
  • TORC1

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Redox State Controls Phase Separation of the Yeast Ataxin-2 Protein via Reversible Oxidation of Its Methionine-Rich Low-Complexity Domain. / Kato, Masato; Yang, Yu San; Sutter, Benjamin M.; Wang, Yun; McKnight, Steven L; Tu, Benjamin P.

In: Cell, Vol. 177, No. 3, 18.04.2019, p. 711-721.e8.

Research output: Contribution to journalArticle

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