Glycophorin A Dimers to Probe Membranes: A 2D-IR Study

用于探测膜的血型糖蛋白 A 二聚体：二维红外研究

• 批准号: 7176826
• 负责人: LOUISE E SINKS
• 金额: $ 4.88万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-01-01 至 2007-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7176826
• 关键词: Amides; Cell physiology; Cholesterol; Coupling; Dimerization; Dimyristoylphosphatidylcholine; Environment; Equilibrium; Frequencies; Glycophorin A; Hydrogen Bonding; Integral Membrane Protein; Label; Lead; Lipid Bilayers; Lipids; Measures; Membrane; Methods; Phase; Photons; Proteins; Resolution; Role; Structure; Techniques; Testing; Time; Vesicle; Work; dimer; infrared spectroscopy; protein structure; research study; time use; two-dimensional; van der Waals force

DESCRIPTION (provided by applicant): 2D-IR experiments are proposed to study the equilibrium structure and dynamics of the transmembrane protein Glycophorin A (GpA) in several lipid bilayer environments. Glycophorin A dimerizes through weak van der Waals forces and CalphaH...O hydrogen bonds. It is expected that these weak associations are easily disrupted as the environment is changed. Thus, 2D-IR studies examining the interactions between the residues on opposite strands will reveal information about how the structure of GpA changes as the environment changes. Several lipid bilayers will be studied, both a dimyristoylphosphatidylcholine (DMPC) membrane vesicle and a DMPC/cholesterol vesicle, to probe how lipid composition influences the structure, and thus function, of transmembrane protein. This work will test hypotheses about the role of lipid microdomains or "rafts" on protein structure. Single and Dual Frequency 2D-IR photon echo experiments will be performed on isotopically labeled GpA in different lipid phases to determine which interactions are most sensitive to environment. Transmembrane proteins are not easily probed by conventional techniques, and the influence of membrane composition on transmembrane structure and function is not well understood. Since many transmembrane proteins critical to cell function, understanding the interplay between membrane environment and protein structure is vitally important.

描述(申请人提供)：2D-IR实验是为了研究跨膜蛋白糖蛋白A(GPA)在几种脂类双层环境中的平衡结构和动力学。血糖素A通过弱的范德华作用力和CalphaH…O氢键进行二聚。预计随着环境的变化，这些弱关联很容易被破坏。因此，2D-IR研究相反链上残基之间的相互作用将揭示GPA的结构如何随着环境变化而变化的信息。我们将研究几种脂质双层，包括二甲基磷脂酰胆碱(DMPC)膜小泡和DMPC/胆固醇小泡，以探索脂质组成如何影响跨膜蛋白的结构和功能。这项工作将检验关于脂微域或“筏”在蛋白质结构上的作用的假说。单频和双频2D-IR光子回波实验将在不同的脂相中对同位素标记的GPA进行，以确定哪些相互作用对环境最敏感。跨膜蛋白不容易用常规技术探测，膜组成对跨膜结构和功能的影响也不是很清楚。由于许多跨膜蛋白对细胞功能至关重要，了解膜环境和蛋白质结构之间的相互作用是至关重要的。