The Ensemble of Conformations of Antifreeze Glycoproteins (AFGP8): A Study Using Nuclear Magnetic Resonance Spectroscopy

Cheenou Her, Yin Yeh, Viswanathan V Krishnan

Research output: Contribution to journalArticle

Abstract

The primary sequence of antifreeze glycoproteins (AFGPs) is highly degenerate, consisting of multiple repeats of the same tripeptide, Ala-Ala-Thr*, in which Thr* is a glycosylated threonine with the disaccharide beta-d-galactosyl-(1,3)-alpha-N-acetyl-d-galactosamine. AFGPs seem to function as intrinsically disordered proteins, presenting challenges in determining their native structure. In this work, a different approach was used to elucidate the three-dimensional structure of AFGP8 from the Arctic cod Boreogadussaida and the Antarctic notothenioid Trematomusborchgrevinki. Dimethyl sulfoxide (DMSO), a non-native solvent, was used to make AFGP8 less dynamic in solution. Interestingly, DMSO induced a non-native structure, which could be determined via nuclear magnetic resonance (NMR) spectroscopy. The overall three-dimensional structures of the two AFGP8s from two different natural sources were different from a random coil ensemble, but their "compactness" was very similar, as deduced from NMR measurements. In addition to their similar compactness, the conserved motifs, Ala-Thr*-Pro-Ala and Ala-Thr*-Ala-Ala, present in both AFGP8s, seemed to have very similar three-dimensional structures, leading to a refined definition of local structural motifs. These local structural motifs allowed AFGPs to be considered functioning as effectors, making a transition from disordered to ordered upon binding to the ice surface. In addition, AFGPs could act as dynamic linkers, whereby a short segment folds into a structural motif, while the rest of the AFGPs could still be disordered, thus simultaneously interacting with bulk water molecules and the ice surface, preventing ice crystal growth.

Original languageEnglish (US)
JournalBiomolecules
Volume9
Issue number6
DOIs
StatePublished - Jun 17 2019

Keywords

  • AFGP
  • antifreeze proteins
  • ensemble of structures
  • NMR

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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