Both Ca2+ and Zn2+ are essential for S100A12 protein oligomerization and function

Article English OPEN
Moroz, Olga V. ; Burkitt, Will ; 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)
  • Journal: BMC BIOCHEMISTRY, volume 10, pages 11-11 (issn: 1471-2091, eissn: 1471-2091)
  • Related identifiers: doi: 10.1186/1471-2091-10-11, pmc: PMC2686732
  • Subject: Molecular Biology | QR | QD | Research Article | Biochemistry

Background\ud 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.\ud \ud Results\ud 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.\ud \ud Conclusion\ud 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.
  • References (62)
    62 references, page 1 of 7

    Zimmer DB, Chaplin J, Baldwin A, Rast M: S100-mediated signal transduction in the nervous system and neurological diseases. Cell Mol Biol (Noisy-le-grand) 2005, 51(2):201-214.

    Heizmann CW, Fritz G, Schafer BW: S100 proteins: structure, functions and pathology. Front Biosci 2002, 7:d1356-1368.

    3. Donato R: Intracellular and extracellular roles of S100 proteins. Microsc res tech 2003, 60(6):540-551.

    4. Guignard F, Mauel J, Markert M: Identification and characterization of a novel human neutrophil protein related to the S100 family. Biochem J 1995, 309(Pt 2):395-401.

    5. Marti T, Erttmann KD, Gallin MY: Host-parasite interaction in human onchocerciasis: identification and sequence analysis of a novel human calgranulin. Biochem Biophys Res Commun 1996, 221(2):454-458.

    6. Akpek EK, Liu SH, Thompson R, Gottsch JD: Identification of paramyosin as a binding protein for calgranulin C in experimental helminthic keratitis. Investigative ophthalmology & visual science 2002, 43(8):2677-2684.

    7. Hofmann MA, Drury S, Fu C, Qu W, Taguchi A, Lu Y, Avila C, Kambham N, Bierhaus A, Nawroth P, et al.: RAGE mediates a novel proinflammatory axis: a central cell surface receptor for S100/calgranulin polypeptides. Cell 1999, 97(7):889-901.

    8. Schmidt AM, Yan SD, Yan SF, Stern DM: The multiligand receptor RAGE as a progression factor amplifying immune and inflammatory responses. The Journal of clinical investigation 2001, 108(7):949-955.

    9. Xie J, Reverdatto S, Frolov A, Hoffmann R, Burz DS, Shekhtman A: Structural basis for pattern recognition by the receptor for advanced glycation end products (RAGE). The Journal of biological chemistry 2008, 283(40):27255-27269.

    10. Bierhaus A, Humpert PM, Morcos M, Wendt T, Chavakis T, Arnold B, Stern DM, Nawroth PP: Understanding RAGE, the receptor for advanced glycation end products. J Mol Med 2005, 83(11):876-886.

  • Related Research Results (1)
  • Bioentities (4)
    1odb Protein Data Bank
    1xyd Protein Data Bank
    2psr Protein Data Bank
    3cr2 Protein Data Bank
  • Metrics
    No metrics available
Share - Bookmark