Crystal structure of the Ca2+-form and Ca2+-binding kinetics of metastasis-associated protein, S100A4

Gingras, Alexandre R.; Basran, Jaswir; Prescott, Andrew; Kriajevska, Marina; Bagshaw, Clive R.; Barsukov, Igor L.

doi:10.1016/j.febslet.2008.04.017

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Volume 582, Issue 12 , Pages 1651-1656, 28 May 2008

Crystal structure of the Ca²⁺-form and Ca²⁺-binding kinetics of metastasis-associated protein, S100A4

Edited by Hans Eklund

Alexandre R. Gingras
- Department of Biochemistry, University of Leicester, Henry Wellcome Building, Leicester LE1 9HN, UK
Jaswir Basran
- Department of Biochemistry, University of Leicester, Henry Wellcome Building, Leicester LE1 9HN, UK
Andrew Prescott
- Department of Biochemistry, University of Leicester, Henry Wellcome Building, Leicester LE1 9HN, UK
Marina Kriajevska
- Department of Cancer Studies and Molecular Medicine, University of Leicester, Hodgkin Building, Leicester LE1 9HN, UK
Clive R. Bagshaw
- Department of Biochemistry, University of Leicester, Henry Wellcome Building, Leicester LE1 9HN, UK
Igor L. Barsukov
- School of Biological Sciences, University of Liverpool, BioSciences Building, Liverpool L69 7ZB, UK
- Corresponding author.

Received 20 March 2008; received in revised form 8 April 2008; accepted 9 April 2008. published online 22 April 2008.

Abstract

S100A4 takes part in control of tumour cell migration and contributes to metastatic spread in in vivo models. In the active dimeric Ca²⁺-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 1.5Å X-ray crystal structure of Ca²⁺-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 Ca²⁺ (k_on=3.5μM⁻¹s⁻¹, k_off=20s⁻¹).