Controlling Liquid–Liquid Phase Separation of Cold-Adapted Crystallin Proteins from the Antarctic Toothfish

Jan C. Bierma, Kyle W. Roskamp, Aaron P. Ledray, Andor J. Kiss, C. H.Christina Cheng, Rachel W. Martin

Research output: Contribution to journalArticle

Abstract

Liquid–liquid phase separation (LLPS) of proteins is important to a variety of biological processes both functional and deleterious, including the formation of membraneless organelles, molecular condensations that sequester or release molecules in response to stimuli, and the early stages of disease-related protein aggregation. In the protein-rich, crowded environment of the eye lens, LLPS manifests as cold cataract. We characterize the LLPS behavior of six structural γ-crystallins from the eye lens of the Antarctic toothfish Dissostichus mawsoni, whose intact lenses resist cold cataract in subzero waters. Phase separation of these proteins is not strongly correlated with thermal stability, aggregation propensity, or cross-species chaperone protection from heat denaturation. Instead, LLPS is driven by protein–protein interactions involving charged residues. The critical temperature of the phase transition can be tuned over a wide temperature range by selective substitution of surface residues, suggesting general principles for controlling this phenomenon, even in compactly folded proteins.

Original languageEnglish (US)
Pages (from-to)5151-5168
Number of pages18
JournalJournal of Molecular Biology
Volume430
Issue number24
DOIs
StatePublished - Dec 7 2018

Fingerprint

Crystallins
Crystalline Lens
Proteins
Cataract
Hot Temperature
Biological Phenomena
Temperature
Phase Transition
Organelles
Lenses
Water

Keywords

  • coacervation
  • crystallins
  • eye lens proteins
  • liquid–liquid phase separation
  • psychrophile

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Cite this

Controlling Liquid–Liquid Phase Separation of Cold-Adapted Crystallin Proteins from the Antarctic Toothfish. / Bierma, Jan C.; Roskamp, Kyle W.; Ledray, Aaron P.; Kiss, Andor J.; Cheng, C. H.Christina; Martin, Rachel W.

In: Journal of Molecular Biology, Vol. 430, No. 24, 07.12.2018, p. 5151-5168.

Research output: Contribution to journalArticle

Bierma, Jan C. ; Roskamp, Kyle W. ; Ledray, Aaron P. ; Kiss, Andor J. ; Cheng, C. H.Christina ; Martin, Rachel W. / Controlling Liquid–Liquid Phase Separation of Cold-Adapted Crystallin Proteins from the Antarctic Toothfish. In: Journal of Molecular Biology. 2018 ; Vol. 430, No. 24. pp. 5151-5168.
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