STRUCTURAL & ENERGETIC PRINCIPLES OF MEMBRANE PROTEINS

描述(改编自摘要)：对结构能量学的理解 膜蛋白远远落后于可溶性蛋白。在某种程度上，这是 由于在原子分辨率下已知的膜蛋白质结构的稀有。 然而，同样负责任的是缺乏定量热力学。 关于膜蛋白折叠和组装的信息。 正在提议的工作将提供关于特异度和 膜蛋白中螺旋-螺旋缔合的稳定性。实验性的 方法将产生详细的结构和热力学分析 血糖素跨膜结构域二聚体。使用新的热力学测量工具 超速离心法将允许对序列进行定量评估 二聚体稳定性依赖于大量的位点特异性突变体。结构 溶液核磁共振测定同一突变体洗涤剂胶束中的 提供了一个结构框架，可在此基础上从实验上理解 观察对单体二聚体平衡的影响。这些原则来自于 结构和热力学测量的集成将是 整合到现有的计算算法中，以改进其 在膜蛋白的建模、预测和设计方面的表现。

DESCRIPTION (Adapted from abstract): Understanding of structural energetics of membrane proteins lags far behind that of soluble proteins. In part, this is due to the rarity of membrane protein structures known at atomic resolution. Equally responsible, however, is the lack of quantitative thermodynamic information on membrane protein folding and assembly. The work being proposed will provide data concerning the specificity and stability of helix-helix associations in membrane proteins. The experimental approach will produce a detailed structural and thermodynamic analysis of the glycophorin transmembrane domain dimer. Novel thermodynamic measurements using ultracentrifugation will permit a quantitative assessment of the sequence dependence of dimer stability through numerous site specific mutants. Structure determination by solution NMR in detergent micelles of the same mutants will provide a structural framework on which to understand the experimentally observed effects on the monomer dimer equilibrium. Principles that emerge from the integration of the structural and thermodynamic measurements will be incorporated into existing computational algorithms to improve their performance in modeling, prediction, and design efforts for membrane proteins.