The crystal structure of metal-free human EF-hand protein S100A3 at 1.7-A resolution.
S100A3 is a unique member of the EF-hand superfamily of Ca(2+)-binding proteins. It binds Ca(2+) with poor affinity (K(d) = 4-35 mm) but Zn(2+) with exceptionally high affinity (K(d) = 4 nm). This high affinity for Zn(2+) is attributed to the unusual high Cys content of S100A3. The protein is ... highly expressed in fast proliferating hair root cells and astrocytoma pointing toward a function in cell cycle control. We determined the crystal structure of the protein at 1.7 A. The high resolution structure revealed a large distortion of the C-terminal canonical EF-hand, which most likely abolishes Ca(2+) binding. The crystal structure of S100A3 allows the prediction of one putative Zn(2+) binding site in the C terminus of each subunit of S100A3 involving Cys and His residues in the coordination of the metal ion. Zn(2+) binding induces a large conformational change in S100A3 perturbing the hydrophobic interface between two S100A3 subunits, as shown by size exclusion chromatography and CD spectroscopy.
Mesh Terms:
Amino Acid Sequence, Androstadienes, Binding Sites, Calcium, Calcium-Binding Proteins, Circular Dichroism, Crystallography, X-Ray, Cysteine, Dimerization, EF Hand Motifs, Escherichia coli, Histidine, Humans, Hydrogen Bonding, Kinetics, Models, Molecular, Molecular Sequence Data, Protein Binding, Protein Conformation, Protein Structure, Tertiary, S100 Proteins, Signal Transduction, Zinc
Amino Acid Sequence, Androstadienes, Binding Sites, Calcium, Calcium-Binding Proteins, Circular Dichroism, Crystallography, X-Ray, Cysteine, Dimerization, EF Hand Motifs, Escherichia coli, Histidine, Humans, Hydrogen Bonding, Kinetics, Models, Molecular, Molecular Sequence Data, Protein Binding, Protein Conformation, Protein Structure, Tertiary, S100 Proteins, Signal Transduction, Zinc
J. Biol. Chem.
Date: Sep. 06, 2002
PubMed ID: 12045193
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