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.

钙调节耦合到诸如收缩，分泌，施肥，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中。 这些功能的核心是钙充当蛋白质构象变化的强大触发因素的能力。在钙调节的过程中，可以结合45个以上钙离子的Cal序列蛋白（CSQ），并且在内质网中发现的其他类似的蛋白质和核质网（SR）作为钙储存蛋白。 已经进行了许多物理化学研究，以阐明这些异常蛋白质钙调节钙调节的结构/功能关系。但是，这些研究受到缺乏详细的结构信息的限制，直到最近CSQ的分子结构最近进行。观察到的结构已经成熟，对CSQ功能的详细机制以及钙调节基础的结构变化有影响。 根据这种新的基于结构的结构/功能模型，随着钙水平的增加，SR腔的单价离子（H，K和Na）水平降低，CSQ聚合物或聚集体的形成伴随形成和高容量的钙结合。 这项研究的重点是使用物理化学方法和重组遗传技术直接测试分子细节。基于原子分辨率结构和生物化学数据，CSQ折叠的重要性和聚合在生理功能方面的重要性以及在CSQ和其他相关蛋白内的结构域的作用。