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

JOURNAL OF MOLECULAR BIOLOGY

卷:430

Article

Bierma, Jan C.¹  Roskamp, Kyle W.²  Ledray, Aaron P.¹  Kiss, Andor J.³  Cheng, C. -H. Christina⁴  Martin, Rachel W.^1,2 

[1] Univ Calif Irvine, Dept Mol Biol & Biochem, Irvine, CA 92697 USA

[2] Univ Calif Irvine, Dept Chem, Irvine, CA 92697 USA

[3] Miami Univ, Ctr Bioinformat & Funct Genom, Oxford, OH 45056 USA

[4] Univ Illinois, Dept Anim Biol, Urbana, IL 61801 USA

关键词: liquid liquid phase separation;    coacervation;    crystallins;    eye lens proteins;    psychrophile;   

DOI  :  10.1016/j.jmb.2018.10.023

来源: Elsevier

【 摘 要 】

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 gamma-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. (C) 2018 Elsevier Ltd. All rights reserved.

【 授权许可】

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