STRUCTURE/FUNCTION OF PHOSPHOLAMBAN IN MEMBRANES

膜中磷苯班的结构/功能

• 批准号: 2545322
• 负责人: Melanie J Cocco
• 金额: $ 2.92万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-10-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2545322
• 关键词: acidity /alkalinity; binding proteins; calcium flux; calcium transporting ATPase; cell membrane; conformation; cytoplasm; infrared spectrometry; interferometry; intermolecular interaction; membrane proteins; membrane structure; muscle cells; muscle contraction; muscle relaxation; myocardium; nuclear magnetic resonance spectroscopy; phospholamban; phosphorylation; physical model; protein kinase A; protein purification; protein structure function; sarcoplasmic reticulum; synthetic peptide

The mechanism of cardiac muscle contraction and relaxation depends on the flux of Ca2+ ions between the cytoplasm and sarcoplasmic reticulum (SR) within the myocytes. Phospholamban has a key role in Ca2+ transport by regulating the Ca2+ ATPase in SR membranes and by functioning as a Ca2+ selective channel. Phosphorylation of phospholamban is the event that determines to which cellular locality the Ca2+ ions will be directed and consequently the contractile state of the muscle tissue. The phospholamban channel is formed by five peptides and a structural model has been developed by researchers at Yale which predicts interhelical contacts consistent with mutagenesis results. The proposed work will test this model and provide atomic-level information on the effect of phosphorylation of the complex in a membrane environment. Specifically, MAS NMR and FTIR data will be collected on phosphorylated and nonphosphorylated samples labeled with 13C at unique positions. An understanding of the structure of the channel should provide insight into the mechanisms of ion flux and selectivity. Additionally, phospholamban may serve as a useful model for larger, more complex ion channels.

心肌收缩和舒张的机制取决于 细胞质和肌浆网 (SR) 之间的 Ca2+ 离子通量 肌细胞内。 Phospholamban 在 Ca2+ 转运中发挥着关键作用 调节 SR 膜中的 Ca2+ ATPase 并发挥 Ca2+ 的作用 选择性渠道。受磷蛋白的磷酸化是这样的事件 确定 Ca2+ 离子将被引导到哪个细胞位置，并且 因此肌肉组织的收缩状态。这 受磷蛋白通道由五种肽和结构模型形成 由耶鲁大学的研究人员开发，预测螺旋间 接触与诱变结果一致。拟议的工作将测试 该模型并提供有关效果的原子级信息 复合物在膜环境中的磷酸化。具体来说， MAS NMR 和 FTIR 数据将收集磷酸化和 非磷酸化样品在独特位置用 13C 标记。一个 了解渠道的结构应该有助于深入了解 离子通量和选择性的机制。此外，受磷蛋白 可以作为更大、更复杂离子通道的有用模型。