Crystal-structure and biochemical characterization of recombinant human calcyphosine delineates a novel EF-hand-containing protein family.
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.
Dong
Hui
H
Laboratory of Structural Biology, Tsinghua University, Beijing 100084, China.
Li
Xin
X
Lou
Zhiyong
Z
Xu
Xiaoling
X
Su
Dan
D
Zhou
Xiaohong
X
Zhou
Weihong
W
Bartlam
Mark
M
Rao
Zihe
Z
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000737:chemistry* / Q000145:classification / Q000235:genetics / Q000378:metabolism; D002147:Calmodulin / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000378:metabolism; D018360:Crystallography, X-Ray; D020832:EF Hand Motifs; D019143:Evolution, Molecular; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
C059605:CAPS protein, human; D002135:Calcium-Binding Proteins; D002147:Calmodulin; D011994:Recombinant Proteins; D002118:Calcium