BIOORGANIC MODELS FOR TRANSMEMBRANE PROTEINS

跨膜蛋白的生物有机模型

• 批准号: 6387072
• 负责人: JAMES D LEAR
• 金额: $ 27.26万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-30 至 2004-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6387072
• 关键词: bacteriorhodopsins; bioenergetics; chemical models; lipid bilayer membrane; membrane proteins; micelles; peptide chemical synthesis; phospholamban; protein structure function; thermodynamics; water solubility

Description: (Applicant's abstract) The energetics governing the folding and function of membrane proteins is less well understood than for water-soluble ones. Thus, while there are abundant data concerning the free energy associated with the burial of an apolar group or the formation of a hydrogen bond in water-soluble proteins, such data are virtually non-existent for membrane proteins. We will determine how amino acid substitutions in the membrane protein bacteriorhodopsin affect its free energy of stabilization. It has been hypothesized that although water-soluble and membrane proteins differ greatly in the polarity of water-facing versus membrane lipid-facing residues, their interior side-chain packing and residue polarities are highly similar. To test this guiding hypothesis we will convert water-soluble proteins into membrane-soluble proteins and vice versa. Our specific aims, then, are: - Aim 1. Membrane-soluble versions of the water-soluble coiled-coil peptide, GCN4-P1, will be designed, synthesized and characterized in micelles and bilayers. - Aim 2. We will determine the effect of amino acid substitutions on the thermodynamic stability of bacteriorhodopsin. - Aim 3. We will design and characterize a water-soluble version of phospholamban, a 57-residue membrane protein that forms transmembrane pentamers. In each case, the thermodynamic properties of the proteins will be thoroughly examined to provide a deeper, quantitative understanding of membrane protein structure.

描述：（申请人的摘要）控制折叠和折叠的能量学 膜蛋白的功能不如水溶性蛋白那么了解 那些。因此，虽然有大量关于相关自由能的数据 随着非极性基团的掩埋或氢键的形成 水溶性蛋白质，这样的数据对于膜来说几乎不存在 蛋白质。我们将确定膜中的氨基酸取代如何 蛋白质细菌视紫红质影响其稳定的自由能。它一直 假设虽然水溶性蛋白和膜蛋白差异很大 在面向水的极性与面向膜脂质的残基的极性中，它们 内部侧链堆积和残基极性高度相似。测试 根据这一指导性假设，我们将把水溶性蛋白质转化为 膜溶性蛋白质，反之亦然。那么，我们的具体目标是： - 目标 1. 水溶性卷曲螺旋肽的膜溶性版本， GCN4-P1，将在胶束中进行设计、合成和表征 双层。 - 目标 2. 我们将确定氨基酸取代对 细菌视紫红质的热力学稳定性。 - 目标 3. 我们将设计并表征水溶性版本 受磷蛋白，一种具有 57 个残基的膜蛋白，可形成跨膜 五聚体。在每种情况下，蛋白质的热力学性质将是 彻底检查以提供对膜更深入、定量的了解 蛋白质结构。