Distinct lipid-binding properties of closely related peroxiredoxin isozymes Prx1 and Prx2

Peroxiredoxin 2 (Prx2) is a ubiquitous 2-Cys peroxiredoxin that exhibits functional changes through stress-dependent oligomerization. Prx2 has also been reported to interact with lipids and change their functions. In this study, we examined the lipid-binding properties of Prx2 by comparison with Prx1, a highly homologous isozyme. Despite retaining all positively charged amino acid residues previously identified as important for binding to negatively charged phospholipids in Prx2, Prx1 did not interact with negatively charged phospholipids and failed to form lipid-dependent oligomers under conditions in which Prx2 readily assembled into lipid-containing complexes. This finding reveals an unexpected functional divergence between the two closely related isozymes. Further analyses demonstrated that neither additional positively charged residues unique to Prx2 nor differences in surface electrostatic properties are sufficient to explain this lipid-binding specificity. These results indicate that lipid binding by Prx2 cannot be explained solely by primary sequence conservation or surface charge distribution. Our findings highlight isozyme-specific regulation of lipid-dependent oligomerization within the peroxiredoxin family.