STRUCTURE/FUNCTION OF PHOSPHOLAMBAN IN MEMBRANES

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 在肌细胞内。受磷蛋白在Ca2+转运中起关键作用， 调节SR膜中的Ca2+ ATP酶，并通过作为Ca2+ ATP酶发挥作用， 选择频道受磷蛋白的磷酸化是 确定Ca2+离子将被引导到哪个细胞位置， 从而影响肌肉组织的收缩状态。的 受磷蛋白通道由五种肽和一种结构模型形成 是由耶鲁大学的研究人员开发的， 接触与诱变结果一致。拟议的工作将测试 该模型并提供关于 在膜环境中的复合物的磷酸化。具体地说， MAS NMR和FTIR数据将收集磷酸化和 在独特位置用13C标记的非磷酸化样品。一个 对通道结构的了解应有助于深入了解 离子通量和选择性的机制。此外，受磷蛋白 可以作为更大、更复杂的离子通道的有用模型。

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.