Meeting Abstract

P1.126  Thursday, Jan. 3  Structure-function relationships during temperature changes in the calcium binding protein calsequestrin BROOKE, B.E.; HARRIS, R.C.; HOFFMAN, G.G.; GROVE, T.J.*; Valdosta State University; Valdosta State University; Florida State University; Valdosta State University tjgrove@valdosta.edu

Calsequestrin (CSQ) is found in the sarcoplasmic reticulum (SR) of muscle where it sequesters and releases Ca²⁺ to enable repetitive contraction-relaxation cycles without loss of tension. As Ca²⁺ levels increase within the SR, CSQ monomers fold into three domain structures that are stabilized by cation binding. As Ca²⁺ levels continue to rise, front-to-front and back-to-back dimerization occurs followed by polymerization. While CSQ has been examined in mammals, much less is known about the response of CSQ to temperature variations in poikilothermic teleosts. The mummichog, Fundulus heteroclitus,, experiences both long-term (seasonal) and rapid (tidal) temperature changes. We are interested in examining how CSQ maintains functional homeostasis in the face of variable physiological temperatures. To this end, we determined the partial amino acid sequence of CSQ from F. heteroclitus glycolytic muscle. This CSQ has a high similarity to rabbit skeletal and cardiac muscle CSQ (88% and 90%, respectively). Molecular modeling of F. heteroclitus CSQ based on the crystal structure of rabbit cardiac CSQ indicates that front-to-front dimerization of F. heteroclitus CSQ involves fewer salt bridges within the monomer-monomer interface, suggesting a decrease in stability for the teleost CSQ dimer. Interestingly, F. heteroclitus CSQ folding is much more favorable than rabbit CSQ (9,639 kJ/mol compared to 15,390 kJ/mol) when the energy of the folded molecule is calculated. Future experiments will test the hypothesis that the interplay of these two characteristics enables CSQ to maintain function at the physiological temperatures of F. heteroclitus.