The unique C terminus of the calcineurin isoform CNAβ1 confers non-canonical regulation of enzyme activity by Ca²⁺ and calmodulin.

ABSTRACT: Calcineurin, the conserved Ca²⁺/calmodulin-regulated phosphatase and target of immunosuppressants, plays important roles in the circulatory, nervous, and immune systems. Calcineurin activity strictly depends on Ca²⁺ and Ca²⁺-bound calmodulin (Ca²⁺/CaM) to relieve autoinhibition of the catalytic subunit (CNA) by its C terminus. The C terminus contains two regulatory domains, the autoinhibitory domain (AID) and calmodulin-binding domain (CBD), which block the catalytic center and a conserved substrate-binding groove, respectively. However, this mechanism cannot apply to CNAβ1, an atypical CNA isoform generated by alternative 3'-end processing, whose divergent C terminus shares the CBD common to all isoforms, but lacks the AID. We present the first

SUBMITTER: Bond R 

PROVIDER: S-EPMC5633132 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature