title: Crystal structure of the Ca(2+)-form and Ca(2+)-binding kinetics of metastasis-associated protein, S100A4.
abstract: S100A4 takes part in control of tumour cell migration and contributes to metastatic spread in in vivo models. In the active dimeric Ca(2+)-bound state it interacts with multiple intracellular targets. Conversely, oligomeric forms of S100A4 are linked with the extracellular function of this protein. We report the 1.5A X-ray crystal structure of Ca(2+)-bound S100A4 and use it to identify the residues involved in target recognition and to derive a model of the oligomeric state. We applied stopped-flow analysis of tyrosine fluorescence to derive kinetics of S100A4 activation by Ca(2+) (k(on)=3.5 microM(-1)s(-1), k(off)=20s(-1)).
authors.affiliation: Department of Biochemistry, University of Leicester, Henry Wellcome Building, Leicester LE1 9HN, UK.
authors.forename: Alexandre R
authors.initials: AR
authors.lastname: Gingras
authors.forename: Jaswir
authors.initials: J
authors.lastname: Basran
authors.forename: Andrew
authors.initials: A
authors.lastname: Prescott
authors.forename: Marina
authors.initials: M
authors.lastname: Kriajevska
authors.forename: Clive R
authors.initials: CR
authors.lastname: Bagshaw
authors.forename: Igor L
authors.initials: IL
authors.lastname: Barsukov
mesh_terms: D000595:Amino Acid Sequence; D002118:Calcium / Q000737:chemistry*; D018360:Crystallography, X-Ray; D005453:Fluorescence; D006801:Humans; D007700:Kinetics; D008024:Ligands; D008969:Molecular Sequence Data; D009362:Neoplasm Metastasis; D011485:Protein Binding; D011487:Protein Conformation; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000737:chemistry*; D014443:Tyrosine / Q000032:analysis
chemical_list: D008024:Ligands; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C077591:S100A4 protein, human; D014443:Tyrosine; D002118:Calcium