Calsequestrin, a Reversible Calcium Conducting Polymer

Calsequestrin，一种可逆钙导电聚合物

• 批准号: 0117192
• 负责人: ChulHee Kang
• 金额: $ 33万
• 依托单位: Washington State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-01 至 2005-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0117192&HistoricalAwards=false
• 关键词: Calsequestrin; Reversible; Calcium; Conducting; Polymer

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.

钙调节与细胞收缩、分泌、受精、增殖、新陈代谢、心跳和记忆等复杂的细胞功能密切相关。这些功能的中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，钙调素蛋白(CSQ)以及内质网和肌浆网(SR)中发现的其他类似蛋白作为钙储存蛋白发挥作用。许多物理化学研究已经被用来阐明与这些不寻常的蛋白质有关的钙调节的结构/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。观察到的结构已经成熟，对CSQ功能的详细机制和钙调节的结构变化具有重要意义。根据这一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)水平的下降，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遗传技术直接检测分子细节，基于原子分辨结构和生化数据，研究CSQ折叠和聚合对生理功能的意义，以及CSQ结构域在CSQ和其他相关蛋白质中的作用。