Protein Disulfide Isomerase (PDIb') family, Calsequestrin subfamily, C-terminal TRX-fold domain; Calsequestrin is the major calcium storage protein in the sarcoplasmic reticulum (SR) of skeletal and cardiac muscle. It stores calcium ions in sufficient quantities (up to 20 mM) to allow repetitive contractions and is essential to maintain movement, respiration and heart beat. A missense mutation in human cardiac calsequestrin is associated with catecholamine-induced polymorphic ventricular tachycardia (CPVT), a rare disease characterized by seizures or sudden death in response to physiologic or emotional stress. Calsequestrin is a highly acidic protein with up to 50 calcium binding sites formed simply by the clustering of two or more acidic residues. The monomer contains three redox inactive TRX-fold domains. Calsequestrin is condensed as a linear polymer in the SR lumen and is membrane-anchored through binding with intra-membrane proteins triadin, junctin and ryanodine receptor (RyR) Ca2+ release channel. In addition to its role as a calcium ion buffer, calsequestrin also regulates the activity of the RyR channel, coordinating the release of calcium ions from the SR with the loading of the calcium store. The C-terminal TRX-fold domain (or domain III) mediates back-to-back dimer interaction and also contriubutes to the front-to-front dimer interface, both of which are important features in the formation of calsequestrin polymers.
Protein Disulfide Isomerase (PDIb') family, Calsequestrin subfamily, C-terminal TRX-fold domain; Calsequestrin is the major calcium storage protein in the sarcoplasmic reticulum (SR) of skeletal and cardiac muscle. It stores calcium ions in sufficient quantities (up to 20 mM) to allow repetitive contractions and is essential to maintain movement, respiration and heart beat. A missense mutation in human cardiac calsequestrin is associated with catecholamine-induced polymorphic ventricular tachycardia (CPVT), a rare disease characterized by seizures or sudden death in response to physiologic or emotional stress. Calsequestrin is a highly acidic protein with up to 50 calcium binding sites formed simply by the clustering of two or more acidic residues. The monomer contains three redox inactive TRX-fold domains. Calsequestrin is condensed as a linear polymer in the SR lumen and is membrane-anchored through binding with intra-membrane proteins triadin, junctin and ryanodine receptor (RyR) Ca2+ release channel. In addition to its role as a calcium ion buffer, calsequestrin also regulates the activity of the RyR channel, coordinating the release of calcium ions from the SR with the loading of the calcium store. The C-terminal TRX-fold domain (or domain III) mediates back-to-back dimer interaction and also contriubutes to the front-to-front dimer interface, both of which are important features in the formation of calsequestrin polymers.