Calsequestrin, a Reversible Calcium Conducting Polymer

Washington State University, Pullman WA

Investigators

Abstract

Calcium regulation is coupled to critically important cellular processes in such complex cellular functions as contraction, secretion, fertilization,proliferation, metabolism, heartbeat and memory. Central to these functions is the ability of calcium to act as a powerful trigger of protein conformational change. In this process of calcium regulation, calsequestrin protein (CSQ), which can bind more than 45 calcium ions,and other similar proteins found in the endoplasmic reticulum and sarcoplasmic reticulum (SR), serve as calcium storage proteins. Many physico-chemical studies have been conducted to elucidate structure/function relationships regarding calcium regulation by these unusual proteins. But those studies were limited by a lack of detailed structural information until the molecular structure of CSQ was determined recently.The observed structure is ripe with implications for the detailed mechanism of CSQ function and the structural changes that underlie calcium regulation. According to this new, structure-based structure/function model,as the calcium levels increase and monovalent ion (H,K,and Na)levels decrease in the SR lumen,there is a concomitant formation of CSQ polymers or aggregates and high capacity calcium binding. The focus of the research is to directly test the molecular details using both physical chemistry methods and recombinant genetic techniques.Based on the atomic resolution structures and biochemical data,the significance of CSQ folding and polymerization with respect to physiological function and the role of structural domains within the CSQ and other related proteins will be investigated.