Structure Changes of Ion-motive ATPases

描述（由申请人提供）：拟研究的重点是SERCA钙泵和NKA钠泵。这是一类叫做“离子驱动ATP酶”的蛋白质中的两种，这种酶利用ATP的能量将离子泵过细胞膜。离子泵在所有细胞中都起着重要作用，这些酶的功能紊乱与人类疾病有关，包括心力衰竭。提出的研究将使用先进的荧光方法来测量活心肌细胞中离子泵的结构和运动。我们将测试三个主要假设：1)离子泵经历了非常大的结构变化。2)这些大的缓慢变化是由快速的蛋白质动力学调节的。3)监管合作伙伴以快速动力学不断地与泵结合和解除结合。通过测量活心肌细胞中atp酶的结构和运动，我们将对衰竭心肌中被破坏的机制有新的认识。

DESCRIPTION (provided by applicant): The proposed research focuses on the SERCA calcium pump and the NKA sodium pump. These are two of a class of proteins called "Ion-motive ATPases", enzymes that use the energy of ATP to pump ions across cell membranes. Ion pumps play an important role in all cells, and disordered function of these enzymes is associated with human disease, including heart failure. The proposed research will use advanced fluorescence methods to measure the structures and motions of ion pumps in living cardiac muscle cells. We will test three major hypotheses: 1) Ion pumps undergo very large structure changes. 2) These large slow changes are regulated by fast protein dynamics. 3) Regulatory partners continually bind and unbind from the pump with fast kinetics. By measuring ATPase structures and motions in live cardiac cells, we will gain new insight into mechanisms that become disrupted in failing cardiac muscle.