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Structure and Function of the proton-turbine of the ATP-Synthase

ATP 合酶质子涡轮的结构和功能

基本信息

批准号：
7924585
负责人：
PETRA FROMME
金额：
$ 25.74万
依托单位：
ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-09-01 至 2013-08-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): One of the most important proteins in energy transduction is the ATP-Synthase (FOF1). This membrane- bound large protein complex is present in nearly all organisms and is essential for all higher life on earth, including humans. Slight defects in function, assembly and the degradation pathways of the enzyme play important roles in severe diseases such as the Batten's disease, Alzheimer's disease and the Retinitis Pigmentosa Syndrome. Furthermore, human mitochondrial ATP Synthase is highly regulated in response to cellular energy needs. The aim of this project is to unravel the structure and catalytic mechanism of this enzyme. The ATP Synthase functions as a molecular (nano) motor, thereby catalyzing the synthesis of ATP from ADP and Pi driven by a transmembrane electrochemical potential of protons or sodium ions. The enzyme complex consists of two distinct structural and functional domains: A membrane intrinsic proton translocation system (the FO part), which is structurally connected by at least two "stalks" to the membrane extrinsic domain (the F1 part), which in turn harbors the nucleotide binding sites. While several structures of the membrane extrinsic F1 part and individual protein subunits of the ion conduction FO part have been determined by X-ray structure crystallography, the molecular elucidation of the coupling mechanism still suffers from the lack of information on the structure of the complete intact ATP Synthase and the membrane intrinsic proton translocation machinery. The goal of this project is to determine the structure of proton turbine of the ATP-Synthase and discover the mechanism of the coupling between proton transfer and ATP-synthesis. The project aims to crystallize the intact ATP Synthase, the proton conducting FO part as well as the c-ring rotor of the enzyme, which differs in its oligomeric state between different organisms. The crystals will be used to determine the structure of the protein complexes by X-ray crystallography. The structural information will form the basis for the discovery of the mechanism of the dynamic energy coupling in the catalytic cycle of the enzyme.

描述（由申请人提供）：atp合成酶（FOF1）是能量转导中最重要的蛋白质之一。这种膜结合的大蛋白复合物几乎存在于所有生物体中，是地球上包括人类在内的所有高等生命所必需的。该酶在功能、组装和降解途径上的轻微缺陷在巴顿病、阿尔茨海默病和色素性视网膜炎综合征等严重疾病中发挥重要作用。此外，人类线粒体ATP合酶在响应细胞能量需求时受到高度调节。该项目的目的是揭示该酶的结构和催化机制。ATP合酶作为分子（纳米）马达，在质子或钠离子的跨膜电化学电位的驱动下，催化ADP和Pi合成ATP。酶复合物由两个不同的结构域和功能域组成：一个膜内质子易位系统（FO部分），它在结构上通过至少两个“茎”连接到膜外结构域（F1部分），后者反过来容纳核苷酸结合位点。虽然通过x射线结构晶体学已经确定了膜外源性F1部分的几个结构和离子传导FO部分的单个蛋白质亚基，但对耦合机制的分子阐明仍然缺乏完整完整的ATP合酶结构和膜内质子易位机制的信息。本项目的目标是确定atp合成酶的质子涡轮结构，发现质子转移与atp合成耦合的机理。本项目旨在结晶完整的ATP Synthase、质子传导FO部分以及酶的c环转子，这些酶在不同的生物体中寡聚状态不同。这些晶体将被用来用x射线晶体学来确定蛋白质复合物的结构。这些结构信息将为发现酶催化循环中动态能量耦合机理奠定基础。