Structure Changes of Ion-motive ATPases

离子动力ATP酶的结构变化

基本信息

批准号：
8313896
负责人：
Seth L Robia
金额：
$ 37.38万
依托单位：
LOYOLA UNIVERSITY CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-08-15 至 2015-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8313896
关键词：
ATP phosphohydrolase Binding Ca(2+)-Transporting ATPase Calcium Calcium ion Cardiac Cardiac Myocytes Cell membrane Cells Chemicals Contracts Coupled Crystallography Data Disease Enzymatic Biochemistry Enzymes Fluorescence Fluorescence Resonance Energy Transfer Fluorescent Probes Freezing Goals Health Heart Heart Diseases Heart failure Heterogeneity Human Hypertrophy In Vitro Individual Ion Pumps Ion Transport Ions Kinetics Life Ligands Measurement Measures Membrane Proteins Methods Molecular Conformation Motion Myocardium Na(+)-K(+)-Exchanging ATPase Outcome Pharmaceutical Preparations Phase Physiological Play Population Positioning Attribute Process Protein Dynamics Proteins Pump Relaxation Research Reticulum Roentgen Rays Role Sampling Shapes Site Spectrum Analysis Structure Structure-Activity Relationship TAC1 gene Techniques Testing Therapeutic Intervention base effective therapy human disease in vivo insight research study theories

项目摘要

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.

描述（由申请人提供）：拟议的研究集中于Serca钙泵和NKA钠泵。这是一类称为“离子 - 含量ATPases”的蛋白质中的两类，这些酶利用ATP的能量在细胞膜上泵送离子。离子泵在所有细胞中都起着重要的作用，这些酶的功能无序功能与人类疾病（包括心力衰竭）有关。拟议的研究将使用晚期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）离子泵发生很大的结构变化。 2）这些较大的缓慢变化受到快速蛋白质动力学的调节。 3）调节伙伴不断与快速动力学结合并与泵绑定。通过测量活心脏细胞中的ATPase结构和运动，我们将获得对心脏肌肉失败的机制的新见解。