Calsequestrin, a Reversible Calcium Conducting Polymer

钙的调节与细胞收缩、分泌、受精、增殖、代谢、心跳和记忆等复杂细胞功能的重要过程密切相关。这些功能的核心是钙作为蛋白质构象变化的强大触发器的能力。在这一钙调节过程中，钙调蛋白（calsequestrin protein， CSQ）与内质网和肌浆网（sarcoplasmic reticulum， SR）中发现的其他类似蛋白一起作为钙储存蛋白，可以结合超过45个钙离子。许多物理化学研究已被用于阐明这些不寻常的蛋白质对钙调节的结构/功能关系。但由于缺乏详细的结构信息，这些研究受到限制，直到最近才确定了CSQ的分子结构。观察到的结构对CSQ功能的详细机制和钙调节基础的结构变化具有成熟的含义。根据这个新的基于结构的结构/功能模型，随着SR管腔中钙水平的增加和单价离子（H，K和Na）水平的降低，CSQ聚合物或聚集体的形成和高容量钙结合。研究的重点是利用物理化学方法和重组基因技术直接测试分子细节。基于原子分辨率结构和生化数据，研究CSQ折叠和聚合在CSQ和其他相关蛋白中的生理功能和结构域的作用。

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 wasdetermined recently.The observed structure is ripe with implications for the detailed mechanismof 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 andbiochemical 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.