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Moroz, Olga V.; Burkitt, William I.; Wittkowski, Helmut; He, Wei; Ianoul, Anatoli; Novitskaya, Vera; Xie, Jingjing; Polyakova, Oxana; Lednev, Igor K.; Shekhtman, Alexander; Derrick, Peter J.; Bjoerk, Per; Foell, Dirk; Bronstein, Igor B. (2009)
Publisher: BioMed Central Ltd.
Journal: BMC Biochemistry
Languages: English
Types: Article
Subjects: QP501-801, QR, Research Article, QD415-436, QD, Animal biochemistry, Biochemistry

Abstract

Background

Human S100A12 is a member of the S100 family of EF-hand calcium-modulated proteins that are associated with many diseases including cancer, chronic inflammation and neurological disorders. S100A12 is an important factor in host/parasite defenses and in the inflammatory response. Like several other S100 proteins, it binds zinc and copper in addition to calcium. Mechanisms of zinc regulation have been proposed for a number of S100 proteins e.g. S100B, S100A2, S100A7, S100A8/9. The interaction of S100 proteins with their targets is strongly dependent on cellular microenvironment.

Results

The aim of the study was to explore the factors that influence S100A12 oligomerization and target interaction. A comprehensive series of biochemical and biophysical experiments indicated that changes in the concentration of calcium and zinc led to changes in the oligomeric state of S100A12. Surface plasmon resonance confirmed that the presence of both calcium and zinc is essential for the interaction of S100A12 with one of its extracellular targets, RAGE – the Receptor for Advanced Glycation End products. By using a single-molecule approach we have shown that the presence of zinc in tissue culture medium favors both the oligomerization of exogenous S100A12 protein and its interaction with targets on the cell surface.

Conclusion

We have shown that oligomerization and target recognition by S100A12 is regulated by both zinc and calcium. Our present work highlighted the potential role of calcium-binding S100 proteins in zinc metabolism and, in particular, the role of S100A12 in the cross talk between zinc and calcium in cell signaling.

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