Metal binding affinity and structural properties of calmodulin-like protein 14 from Arabidopsis thaliana

Protein Sci. 2016 Aug;25(8):1461-71. doi: 10.1002/pro.2942. Epub 2016 May 18.

Abstract

In addition to the well-known Ca(2+) sensor calmodulin, plants possess many calmodulin-like proteins (CMLs) that are predicted to have specific roles in the cell. Herein, we described the biochemical and biophysical characterization of recombinant Arabidopsis thaliana CML14. We applied isothermal titration calorimetry to analyze the energetics of Ca(2+) and Mg(2+) binding to CML14, and nuclear magnetic resonance spectroscopy, together with intrinsic and ANS-based fluorescence, to evaluate the structural effects of metal binding and metal-induced conformational changes. Furthermore, differential scanning calorimetry and limited proteolysis were used to characterize protein thermal and local stability. Our data demonstrate that CML14 binds one Ca(2+) ion with micromolar affinity (Kd ∼ 12 µM) and the presence of 10 mM Mg(2+) decreases the Ca(2+) affinity by ∼5-fold. Although binding of Ca(2+) to CML14 increases protein stability, it does not result in a more hydrophobic protein surface and does not induce the large conformational rearrangement typical of Ca(2+) sensors, but causes only localized structural changes in the unique functional EF-hand. Our data, together with a molecular modelling prediction, provide interesting insights into the biochemical properties of Arabidopsis CML14 and may be useful to direct additional studies aimed at understanding its physiological role.

Keywords: Arabidopsis thaliana; EF-hand; calcium binding; calmodulin-like protein; conformational change; protein stability.

MeSH terms

  • Amino Acid Sequence
  • Arabidopsis / chemistry*
  • Arabidopsis / genetics
  • Arabidopsis / metabolism
  • Arabidopsis Proteins / chemistry*
  • Arabidopsis Proteins / genetics
  • Arabidopsis Proteins / metabolism
  • Binding Sites
  • Calcium / chemistry*
  • Calcium / metabolism
  • Calmodulin / chemistry*
  • Calmodulin / genetics
  • Calmodulin / metabolism
  • Cations, Divalent
  • Cloning, Molecular
  • Conserved Sequence
  • EF Hand Motifs
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Gene Expression
  • Hydrophobic and Hydrophilic Interactions
  • Magnesium / chemistry*
  • Magnesium / metabolism
  • Models, Molecular
  • Mutation
  • Protein Binding
  • Protein Stability
  • Protein Structure, Secondary
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Sequence Alignment

Substances

  • Arabidopsis Proteins
  • Calmodulin
  • Cations, Divalent
  • Recombinant Proteins
  • Magnesium
  • Calcium