Oxidation of CaMKIIα cysteines inhibits autonomous activation induced by phosphorylation.

ABSTRACT: Ca²⁺/calmodulin-dependent protein kinase II α (CaMKIIα) "autonomous" activation induced by Thr286 phosphorylation has a crucial role in synaptic plasticity. Previous studies showed that in Alzheimer's disease brain, CaMKIIα autophosphorylation at Thr286 is reduced while the level of cysteine-oxidized CAMKIIα is elevated. We performed tryptic mapping of the oxidized CaMKIIα and discovered the formation of a disulfide between the N-terminal Cys6 and the regulatory domain Cys280. The apparent pK_a values of Cys6 and Cys280 are 7.1 and 7.7, respectively, lower than the 8.5 for free Cys. The low apparent pK_a of Cys6 facilitates the oxidation of its thiol to the sulfenic acid at physiological pH. The thiolate of Cys280 can then attack the sulfenic acid to form a d

SUBMITTER: Rocco-Machado N 

PROVIDER: S-EPMC11750588 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature