Methionine oxidation by Taurine Chloramine Causes Loss of Function of Cofilin Protein

Thursday, October 11, 2012 — Poster Session IV
2:00 p.m. – 4:00 p.m.	Natcher Conference Center, Building 45	FDA/CBER	OXIDSTRESS-3

Authors

• S Luo
• H Uehara
• E Shacter

Abstract

Taurine chloramine (TnCl) oxidizes cysteine and methionine residues in cofilin, but only cysteine oxidation mediates TnCl-induced apoptosis (Nature Cell Biology 2009, v11, pp1241). Oxidation could possibly affect cofilin’s biological properties in regulating actin dynamics, and an altered actin dynamics has been reported to link to apoptosis. Here we investigated the effect of TnCl-induced oxidation on filament actin regulatory activities of cofilin in vitro. The data indicate that cofilin oxidation almost eliminates its filaments depolymerization ability, and inhibits its binding to filaments. In contrast to the previous finding from cellular studies, neither the reduction of intramolecular disulfide bonds nor the double Cys mutation restored the activities of oxidized cofilin, indicating the oxidation of Met rather than Cys as the main cause of its functional impairment. The observation that only single Met was the main target of oxidation in double Cys mutant led us identify Met-115 as the site responsible for the functional impairment. Oxidation of Met-115 could cause the disruption of the globular-actin binding site, which is required for the function of cofilin under physiological salt conditions. Our finding that Cys oxidation is not responsible for the inactivation of cofilin by TnCl suggests no role of actin dynamics in TnCl-induced apoptosis.

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