Crystal-structure and biochemical characterization of recombinant human calcyphosine delineates a novel EF-hand-containing protein family

J Mol Biol. 2008 Nov 14;383(3):455-64. doi: 10.1016/j.jmb.2008.08.048. Epub 2008 Aug 27.

Abstract

Calcyphosine is an EF-hand protein involved in both Ca(2+)-phosphatidylinositol and cyclic AMP signal cascades, as well as in other cellular functions. The crystal structure of Ca(2+)-loaded calcyphosine was determined up to 2.65 A resolution and reveals a protein containing two pairs of Ca(2+)-binding EF-hand motifs. Calcyphosine shares a highly similar overall topology with calmodulin. However, there are striking differences between EF-hand 4, both N-terminal and C-terminal regions, and interdomain linkers. The C-terminal domain of calcyphosine possesses a large hydrophobic pocket in the presence of calcium ions that might be implicated in ligand binding, while its N-terminal hydrophobic pocket is almost shielded by an additional terminal helix. Calcyphosine is largely monomeric, regardless of the presence of Ca(2+). Differences in structure, oligomeric state in the presence and in the absence of Ca(2+), a highly conserved sequence with low similarity to other proteins, and phylogeny define a new EF-hand-containing family of calcyphosine proteins that extends from arthropods to humans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Calcium / metabolism
  • Calcium-Binding Proteins / chemistry*
  • Calcium-Binding Proteins / classification
  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / metabolism
  • Calmodulin / chemistry
  • Calmodulin / classification
  • Calmodulin / genetics
  • Calmodulin / metabolism
  • Crystallography, X-Ray
  • EF Hand Motifs*
  • Evolution, Molecular
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Nuclear Magnetic Resonance, Biomolecular
  • Protein Structure, Secondary*
  • Protein Structure, Tertiary*
  • Recombinant Proteins / chemistry*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Sequence Alignment
  • Sequence Homology, Amino Acid

Substances

  • CAPS protein, human
  • Calcium-Binding Proteins
  • Calmodulin
  • Recombinant Proteins
  • Calcium

Associated data

  • PDB/3E3R