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Post-translational tyrosine nitration of eosinophil granule toxins mediated by eosinophil peroxidase


Reference:

Ulrich, M., Petre, A., Youhnovski, N., Promm, F., Schirle, M., Schumm, M., Pero, R. S., Doyle, A., Checkel, J., Kita, H., Thiyagarajan, N., Acharya, K. R., Schmid-Grendelmeier, P., Simon, H. U., Schwarz, H., Tsutsui, M., Shimokawa, H., Bellon, G., Lee, J. J., Przybylski, M. and Doring, G., 2008. Post-translational tyrosine nitration of eosinophil granule toxins mediated by eosinophil peroxidase. Journal of Biological Chemistry, 283 (42), pp. 28629-28640.

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Official URL:

http://dx.doi.org/10.1074/jbc.M801196200

Abstract

Nitration of tyrosine residues has been observed during various acute and chronic inflammatory diseases. However, the mechanism of tyrosine nitration and the nature of the proteins that become tyrosine nitrated during inflammation remain unclear. Here we show that eosinophils but not other cell types including neutrophils contain nitrotyrosine-positive proteins in specific granules. Furthermore, we demonstrate that the human eosinophil toxins, eosinophil peroxidase (EPO), major basic protein, eosinophil-derived neurotoxin (EDN) and eosinophil cationic protein (ECP), and the respective murine toxins, are post-translationally modified by nitration at tyrosine residues during cell maturation. High resolution affinity-mass spectrometry identified specific single nitration sites at Tyr(349) in EPO and Tyr(33) in both ECP and EDN. ECP and EDN crystal structures revealed and EPO structure modeling suggested that the nitrated tyrosine residues in the toxins are surface exposed. Studies in EPO-/-, gp91(phox-/-), and NOS-/- mice revealed that tyrosine nitration of these toxins is mediated by EPO in the presence of hydrogen peroxide and minute amounts of NOx. Tyrosine nitration of eosinophil granule toxins occurs during maturation of eosinophils, independent of inflammation. These results provide evidence that post-translational tyrosine nitration is unique to eosinophils.

Details

Item Type Articles
CreatorsUlrich, M., Petre, A., Youhnovski, N., Promm, F., Schirle, M., Schumm, M., Pero, R. S., Doyle, A., Checkel, J., Kita, H., Thiyagarajan, N., Acharya, K. R., Schmid-Grendelmeier, P., Simon, H. U., Schwarz, H., Tsutsui, M., Shimokawa, H., Bellon, G., Lee, J. J., Przybylski, M. and Doring, G.
DOI10.1074/jbc.M801196200
Uncontrolled Keywordscationic protein, crystal-structure, nitric-oxide synthase, cloning, in-vitro identification, major basic-protein, active-site, angstrom resolution, ribonucleolytic, trypanosoma-cruzi
DepartmentsFaculty of Science > Biology & Biochemistry
RefereedYes
StatusPublished
ID Code15562

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