Calsequestrin, a Reversible Calcium Conducting Polymer

钙调节与诸如收缩、分泌、受精、增殖、代谢、心跳和记忆等复杂细胞功能中至关重要的细胞过程相关联。 这些功能的核心是钙作为蛋白质构象变化的强有力触发剂的能力。在这一钙调节过程中，可结合超过45个钙离子的钙螯合蛋白（CSQ）以及在内质网和肌浆网（SR）中发现的其他类似蛋白质充当钙储存蛋白。 已经进行了许多物理化学研究，以阐明这些不寻常的蛋白质对钙调节的结构/功能关系。但这些研究受到缺乏详细结构信息的限制，直到最近确定了CSQ的分子结构。观察到的结构对于CSQ功能的详细机制和钙调节的结构变化具有重要意义。 根据这种新的基于结构的结构/功能模型，随着SR腔中钙水平增加和单价离子（H、K和Na）水平降低，伴随着CSQ聚合物或聚集体和高容量钙结合的形成。 研究重点是利用物理化学方法和重组基因技术直接检测分子细节，基于原子分辨率结构和生化数据，研究CSQ折叠和聚合在生理功能方面的意义以及CSQ和其他相关蛋白质中结构域的作用。

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.