Synergy between Antifreeze Proteins Is Driven by Complementary Ice-Binding

Tehilla Berger, Konrad Meister, Arthur L. Devries, Robert Eves, Peter L. Davies, Ran Drori

Research output: Contribution to journalArticlepeer-review


In some cold-adapted organisms, over a dozen isoforms of antifreeze (glyco)proteins or AF(G)Ps are present. Although these isoforms are structurally similar, their ability to inhibit ice growth varies significantly, and, in some fish, passive isoforms can be much more abundant than the active ones. Laboratory experiments demonstrated more than a decade ago that mixtures of AFP isoforms can exhibit synergistic enhancement of each other's activity. The mechanism of this synergy effect has remained obscure and is addressed here. Using cold-stages, microfluidics, and fluorescence microscopy, the activity of binary mixtures of structurally distinct AF(G)Ps from different fish and plant species was measured. While several mixtures exhibited enhancement, some mixtures exhibited antagonism. These latter mixtures included AF(G)Ps that bind to the same crystal planes, thereby exhibiting competition. Fluorescence microscopy experiments with a synergistic mixture of two isoform types labeled with different dyes showed they bound to different crystal planes. These results helped develop a kinetic description of the mechanism by which AF(G)Ps achieve synergy. The requirements of an active isoform include high adsorption rates, and prism plane binding, while passive isoforms usually bind to a pyramidal plane at slower rates. For synergy to occur, an active isoform first binds to the faster growing prism plane. This binding slows the advancement of the prism plane and creates more pyramidal surfaces to which a passive isoform bind. These results, in part, explain the biological observation of isoform distribution in fish, and the physical chemistry of the synergistic crystal growth inhibition by two inhibitors.

Original languageEnglish (US)
Pages (from-to)19144-19150
Number of pages7
JournalJournal of the American Chemical Society
Issue number48
StatePublished - Dec 4 2019

ASJC Scopus subject areas

  • Catalysis
  • General Chemistry
  • Biochemistry
  • Colloid and Surface Chemistry


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