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 journalArticlepeer-review


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
Issue number24
StatePublished - Dec 7 2018


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

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology


Dive into the research topics of 'Controlling Liquid–Liquid Phase Separation of Cold-Adapted Crystallin Proteins from the Antarctic Toothfish'. Together they form a unique fingerprint.

Cite this