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Disulfide Dimerization of Neuronal Calcium Sensor-1: Implications for Zinc and Redox Signaling.


ABSTRACT: Neuronal calcium sensor-1 (NCS-1) is a four-EF-hand ubiquitous signaling protein modulating neuronal function and survival, which participates in neurodegeneration and carcinogenesis. NCS-1 recognizes specific sites on cellular membranes and regulates numerous targets, including G-protein coupled receptors and their kinases (GRKs). Here, with the use of cellular models and various biophysical and computational techniques, we demonstrate that NCS-1 is a redox-sensitive protein, which responds to oxidizing conditions by the formation of disulfide dimer (dNCS-1), involving its single, highly conservative cysteine C38. The dimer content is unaffected by the elevation of intracellular calcium levels but increases to 10-30% at high free zinc concentrations (characteristic of oxidative stress), w

SUBMITTER: Baksheeva VE 

PROVIDER: S-EPMC8623652 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature