STRUCTURE OF PHOSPHOLAMBAN/CALCIUM ATPASE COMPLEX

磷脂酶/钙ATP酶复合物的结构

• 批准号: 2734337
• 负责人: HOWARD S YOUNG
• 金额: $ 1.59万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-12-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2734337
• 关键词: Animalia; X ray crystallography; calcium transporting ATPase; intermolecular interaction; phospholamban; protein structure function; sarcoplasmic reticulum

The long-term objective of the research proposal is to understand the regulation of the Ca2+-ATPase, and its role in the control of contractility in the heart. Phospholamban (PLB) is an integral membrane protein of cardiac muscle, and is the primary regulatory mechanism by which beta-adrenergic stimulation is transduced into a change in myocardial function. Through a presumed interaction with the Ca2+-pumping ATPase of cardiac sarcoplasmic reticulum (SR), phospholamban decreases the affinity of the Ca2+-ATPase for Ca2+. The physiological effect is thought to be altered Ca2+ loading of the SR which is linked to changes in contractility. Understanding this process at the molecular level will allow the design of therapeutic strategies targeting phospholamban in cardiac and smooth muscle, with potential benefits in sports medicine and the treatment of certain disease states (i.e., hypertrophy, congestive heart failure, hypertension, coronary artery disease, and asthma). Therefore, the specific aim of this research project is to characterize the structure of the inhibitory complex between PLB and Ca2+-ATPase. This will be achieved by co-reconstituting PLB and Ca2+-ATPase into a membrane environment at high density and crystallizing the resultant vesicles in the plane of the membrane. The structural interaction between these two proteins will be studied at an anticipated resolution of at least 14 angstroms by frozen hydrated electron microscopy and 3-dimensional helical reconstruction. In parallel, PLB will be reconstituted into a membrane environment at high density and crystallized in the plane of the membrane. The structure of this protein will be studied by frozen hydrated electron microscopy and 3-dimensional reconstruction. These structures will allow us to specifically define the site of PLB binding, the functional form of PLB, and conformational changes associated with PLB binding. Through this information, we will achieve a better understanding of the role of PLB in the regulation of contractility in cardiac muscle.

研究计划的长期目标是了解

项目成果

Co-reconstitution and co-crystallization of phospholamban and Ca(2+)-ATPase.

受磷蛋白和 Ca(2 )-ATPase 的共重构和共结晶。

• DOI: 10.1111/j.1749-6632.1998.tb08260.x
• 发表时间: 1998
• 期刊: Annals of the New York Academy of Sciences
• 影响因子: 5.2
• 作者: Young,HS;Reddy,LG;Jones,LR;Stokes,DL
• 通讯作者: Stokes,DL

Locating phospholamban in co-crystals with Ca(2+)-ATPase by cryoelectron microscopy.

通过冷冻电子显微镜在与 Ca(2)-ATPase 共晶中定位受磷蛋白。

• DOI: 10.1016/s0006-3495(01)75748-7
• 发表时间: 2001
• 期刊: Biophysical journal
• 影响因子: 3.4
• 作者: Young,HS;Jones,LR;Stokes,DL
• 通讯作者: Stokes,DL