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Abstract:
Thymosin β4 (Tβ4), a peptide of 43 amino acids, binds to actin monomers and inhibits filament formation. In preparations of Tβ4 from bovine lung tissue, the peptide is accompanied by a derivative in which the methionine residue in position 6 is replaced by its sulfoxide. Tβ4 sulfoxide inhibits actin polymerization to an extent approximately 20-times less than Tβ4. While an equimolar amount of Tβ4 prevented actin polymerization almost completely, polymerization with the corresponding amount of the sulfoxide proceeded in a manner similar to that of pure actin, except for a slight retardation. We showed that the decrease in the inhibitory activity is reflected by a 20-times lower affinity to actin. Interestingly, under non-polymerizing conditions, the affinity of Tβ4 sulfoxide for actin is as high as that of Tβ4 (approximately 1 μM). In accordance with this, no differences were found between Tβ4 and the sulfoxide in cross-linking experiments with the monomer, where both forms of the peptide yielded similar amounts of a 47-kDa band representing conjugates of actin and β-thymosin, as proved by Western-blotting analysis. Likewise, both, Tβ4 and the sulfoxide retarded the exchange of G-actin-bound nucleotide to similar extents. Although the sulfoxide is presumably a product of autoxidation, it is attractive to speculate that oxidation of the methionine residue in Tβ4 may represent a regulatory switch for starting filament formation in non-muscle cells.
