CRYSTAL-STRUCTURE OF CALSEQUESTRIN FROM RABBIT SKELETAL-MUSCLE SARCOPLASMIC-RETICULUM

Calsequestrin, the major Ca2+ storage protein of muscle, coordinately binds and releases 40-50 Ca2+ ions per molecule for each contraction-r elaxation cycle by an uncertain mechanism. We have determined the stru cture of rabbit skeletal muscle calsequestrin. Three very negative thi oredoxin-like domains surround a hydrophilic center. Each monomer make s two extensive dimerization contacts, both of which involve the appro ach of many negative groups. This structure suggests a mechanism by wh ich calsequestrin may achieve high capacity Ca2+ binding. The suggeste d mechanism involves Ca2+-induced collapse of the three domains and po lymerization of calsequestrin monomers arising from three factors: N-t erminal arm exchange, helix-helix contacts and Ca2+ cross bridges. Thi s proposed structure-based mechanism accounts for the observed couplin g of high capacity Ca2+ binding with protein precipitation.