Zinc binding reverses the calcium-induced arachidonic acid-binding capacity of the S100A8/A9 protein complex.
Analysis of the calcium-induced arachidonic acid (AA) binding to S100A8/A9 revealed that maximal AA binding was achieved at molar ratios of 1 mol S100A8 and 1 mol S100A9 and for values greater than 3 calciums per EF-hand. The AA binding capacity was not induced by the binding of other bivalent cations, such as Zn2+, Cu2+, and Mg2+, to the protein complex. In contrast, the binding of AA was prevented by the addition of either Zn2+ or Cu2+ in the presence of calcium, whereas Mg2+ failed to abrogate the AA binding capacity. The inhibitory effect was not due to blocking the formation of S100A8/A9 as demonstrated by a protein-protein interaction assay. Fluorescence measurements gave evidence that both Zn2+ and Cu2+ induce different conformational changes thereby affecting the calcium-induced formation of the AA binding pocket within the protein complex. Due to the fact that the inhibitory effect of Zn2+ was present at physiological serum concentrations, it is assumed that released S100A8/A9 may carry AA at inflammatory lesions, but not within the blood compartment.
Kerkhoff
C
C
Institute of Experimental Dermatology, Münster, Germany. kerkhoc@uni-muenster.de
Vogl
T
T
Nacken
W
W
Sopalla
C
C
Sorg
C
C
D000943:Antigens, Differentiation / Q000378:metabolism*; D016718:Arachidonic Acid / Q000378:metabolism*; D001665:Binding Sites; D002118:Calcium / Q000494:pharmacology*; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D040501:Calgranulin A; D040502:Calgranulin B; D003300:Copper / Q000494:pharmacology; D020832:EF Hand Motifs; D006801:Humans; D008274:Magnesium / Q000494:pharmacology; D009504:Neutrophils; D011485:Protein Binding / Q000187:drug effects; D011487:Protein Conformation; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D009418:S100 Proteins / Q000378:metabolism; D014364:Tryptophan / Q000737:chemistry; D014443:Tyrosine / Q000737:chemistry; D015032:Zinc / Q000494:pharmacology*
D000943:Antigens, Differentiation; D002135:Calcium-Binding Proteins; D040501:Calgranulin A; D040502:Calgranulin B; D011993:Recombinant Fusion Proteins; D009418:S100 Proteins; D016718:Arachidonic Acid; D014443:Tyrosine; D003300:Copper; D014364:Tryptophan; D008274:Magnesium; D015032:Zinc; D002118:Calcium