Enhancing the activity of a beta-helical antifreeze protein by the engineered addition of coils

Biochemistry. 2004 Sep 21;43(37):11637-46. doi: 10.1021/bi0488909.

Abstract

The effectiveness of natural antifreeze proteins in inhibiting the growth of a seed ice crystal seems to vary with protein size. Here we have made use of the extreme regularity of the beta-helical antifreeze protein from the beetle Tenebrio molitor to explore systematically the relationship between antifreeze activity and the area of the ice-binding site. Each of the 12-amino acid, disulfide-bonded central coils of the beta-helix contains a Thr-Xaa-Thr ice-binding motif. By adding coils to, and deleting coils from, the seven-coil parent antifreeze protein, we have made a series of constructs with 6-11 coils. Misfolded forms of these antifreezes were removed by ice affinity purification to accurately compare the specific activity of each construct. There was a 10-100-fold gain in activity upon going from six to nine coils, depending on the concentration that was compared. Activity was maximal for the nine-coil construct, which gave a freezing point depression of 6.5 C degrees at 0.7 mg/mL, but actually decreased for the 10- and 11-coil constructs. This small loss in activity might result from the accumulation of a slight mismatch between the spacing of the ice-binding threonine residues and the O atoms of the ice lattice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antifreeze Proteins / chemistry*
  • Antifreeze Proteins / genetics
  • Antifreeze Proteins / metabolism*
  • Base Sequence
  • Binding Sites
  • Ice
  • Molecular Sequence Data
  • Protein Isoforms / chemistry
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Protein Structure, Secondary*
  • Protein Structure, Tertiary*
  • Structure-Activity Relationship
  • Temperature
  • Tenebrio / chemistry*

Substances

  • Antifreeze Proteins
  • Ice
  • Protein Isoforms