MODELING OF STRUCTURE OF AN INTEGRAL MEMBRANE PROTEIN AQUAPORIN

整体膜蛋白水通道蛋白的结构建模

• 批准号: 6122386
• 负责人: XICHE HU
• 金额: $ 1.36万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-08-01 至 1999-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6122386
• 关键词: bacteria; bioengineering /biomedical engineering; biomedical resource; human tissue; nucleic acids; proteins; structural biology

Water is an essential component of all living cells and their extracellular surroundings. Transport of water in and out of cells occurs during a variety of important cellular functions such as regulation of body temperature, elimination of toxins, digestion, respiration, circulation, and neural homeostasis. Aquaporin-1 (AQP1) is an integral membrane protein that functions as a specific and constitutively active water conducting channel [92, 93]. We are attempting to predict the structure of AQP1 from human erythrocyte membranes [94] by means of a hierarchical structure prediction approach. In this approach molecular dynamics simulations and energy minimization are combined with conventional structure prediction methods under experimental constraints derived from biochemical and spectroscopical data. AQP1 from human erythrocyte is composed of 269 residues [94] that form six transmembrane helices. Hydropathy analysis was performed to identify the putative transmembrane segments, which were then independently verified by multiple sequence alignment propensity analyses and homology modeling. A consensus assignment for secondary structure was derived from combination of all the prediction methods used. Three dimensional structures for transmembrane helical segments were built by comparative modeling. The resulting tertiary structures were then aggregated into a quaternary structure through molecular dynamics simulations followed by energy minimization under constraints provided by a low resolution three dimensional electron density map measured by electron microscopy [95], site directed mutagenesis and FT Resonance Raman spectra, as well as conservation of residues.

水是所有活细胞及其生命体的重要组成部分 细胞外环境。 水进出细胞的运输 发生在各种重要的细胞功能期间，例如 调节体温、排除毒素、消化、 呼吸、循环和神经稳态。 水通道蛋白-1 (AQP1) 是一种完整的膜蛋白，具有特定的和 本构型活性导水通道 [92, 93]。 我们是 尝试预测人类红细胞 AQP1 的结构 膜[94]通过层次结构预测 方法。 在这种方法中分子动力学模拟和能量 最小化与传统结构预测相结合 源自生化和实验限制的方法 光谱数据。 来自人红细胞的 AQP1 由 269 残基[94]形成六个跨膜螺旋。 水疗 进行分析以确定假定的跨膜 片段，然后通过多个序列独立验证 比对倾向分析和同源建模。 达成共识 二级结构的分配源自所有的组合 使用的预测方法。 三维结构 通过比较建模构建跨膜螺旋段。 然后将所得的三级结构聚合成 随后通过分子动力学模拟得到四级结构 通过低分辨率限制下的能量最小化 电子显微镜测量的三维电子密度图 [95]，定点诱变和 FT 共振拉曼光谱，如 以及残留物的保护。