Ultrafast Processing in Proteins and Other Assemblies

蛋白质和其他组装体的超快处理

• 批准号: 7167153
• 负责人: ROBIN Main HOCHSTRASSER
• 金额: $ 28.11万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 1977
• 资助国家: 美国
• 起止时间: 1977-02-01 至 2010-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7167153
• 关键词: Accounting; Actins; Amides; Biological Process; Cell Surface Receptors; Cell physiology; Class; Classification; Code; Complement; Coupled; Coupling; Deuterium; Drug Delivery Systems; Elements; Equilibrium; Evolution; Frequencies; Genetic; Glycophorin A; Health; Helix (Snails); Human; Hydrogen; Hydrogen Bonding; Imagery; Integral Membrane Protein; Intercept; Ion Channel; Isotope Labeling; Isotopes; Kidney; Kinetics; Knowledge; Label; Leucine Zippers; Lipids; Location; Measurement; Measures; Mediating; Membrane; Membrane Proteins; Methods; Modeling; Motion; Object Attachment; Organism; Oxidation-Reduction; Pathway interactions; Peptides; Population; Process; Proline; Proteins; Purpose; Research; Research Personnel; Resolution; Robin bird; Spectrum Analysis; Structure; System; Temperature; Testing; Theoretical model; Time; Translating; Transmembrane Domain; Work; base; cytochrome c; design; dimer; ear helix; gastrointestinal epithelium; infrared spectroscopy; interfacial; molecular dynamics; novel; novel strategies; peptide structure; programs; protein folding; protein structure; research study; structural biology; theories; three dimensional structure; tool; two-dimensional; villin

DESCRIPTION (provided by applicant): A residue level visualization of how protein structures change with time for transmembrane (TM) helices, fast folding proteins and elements of secondary structure will be found by two dimensional infrared spectroscopy (2D IR) a new, powerful method of structural biology. Isotopic labeling of peptides and proteins enhances the spatial resolution of 2D IR and extends it to larger peptides. Weak bonds involved at the helix-helix interfaces of TM sections of Glycophorin A will be accessed to obtain the motions of groups in the interface regions and discover how they stabilize helix-helix interactions in TM proteins. 2D IR exposes lipid fluctuations in terms of spatial arrangements across the membrane. 2D IR of hydrophobic effects, polarity, hydrogen bonding and other weak interactions between buried residues enlighten the mechanisms and structural basis of helix association. The 2D IR with multiple IR frequencies, accesses the hydrophobic interface, correlations between fluctuations at different spatial locations and the N-H/N-D exchange in transmembrane helices. Protein subdomains that fold independently are important tools for solving the folding problem. 2D IR on fast non-exponential folders will permit access to the real time evolution of secondary structure and challenge all atom molecular dynamics of the villin headpiece from the actin-bundling protein villin, which is implicated in the epithelium of the gut and kidney. The folding pathway will be accessed by 2D IR of isotope labeled helices and hydrophobic core. On-pathway intermediates in the redox protein, cytochrome-c, will be examined with novel temperature induced pH jumps. A description of the folding of designed peptides will be sought by 2D IR, to visualize how they assemble and strengthen relations to theory. The research involves membrane proteins which are vital components of the cell physiology: they include cell-surface receptors, ion channels, transporters and redox proteins. Integral membrane proteins account for nearly one-quarter of all coding sequences in higher organisms, and more than half of all commercial drugs target this class of proteins. Despite this, study of their 3D structures and their dynamics remains limited. Protein folding is highly relevant, because it is a key step in the conversion of genetic information into biological function of all types and therefore its control is an essential part of understanding human health.

描述(申请人提供)：二维红外光谱(2D IR)是一种新的、功能强大的结构生物学方法，它可以直观地显示跨膜(TM)螺旋、快速折叠蛋白质和二级结构元素的蛋白质结构随时间变化的残基水平。多肽和蛋白质的同位素标记提高了2D IR的空间分辨率，并将其扩展到更大的多肽。涉及糖蛋白A的TM区段螺旋-螺旋界面的弱键将被访问，以获得界面区域中基团的运动，并发现它们如何稳定TM蛋白质中的螺旋-螺旋相互作用。2D IR揭示了跨膜的空间排列的脂类波动。埋藏残基之间的疏水效应、极性、氢键等弱相互作用的二维红外光谱揭示了螺旋缔合的机制和结构基础。具有多个红外频率的2D IR访问疏水界面、不同空间位置的涨落之间的关联以及跨膜螺旋中的N-H/N-D交换。独立折叠的蛋白质亚域是解决折叠问题的重要工具。快速非指数文件夹上的2D IR将允许访问二级结构的实时演变，并挑战与肠道和肾脏上皮有关的肌动蛋白捆绑蛋白Villin的所有原子分子动力学。折叠途径将通过同位素标记的螺旋和疏水核心的2D IR进行访问。氧化还原蛋白中的中间产物细胞色素-c将用新的温度引起的pH跳跃进行检测。2D IR将寻求设计的多肽折叠的描述，以可视化它们如何组装并加强与理论的关系。这项研究涉及细胞生理学的重要组成部分--膜蛋白：它们包括细胞表面受体、离子通道、转运体和氧化还原蛋白。在高等生物体中，完整的膜蛋白占所有编码序列的近四分之一，超过一半的商业药物针对这类蛋白。尽管如此，对它们的3D结构和动力学的研究仍然有限。蛋白质折叠具有很高的相关性，因为它是将遗传信息转化为各种生物功能的关键步骤，因此它的控制是了解人类健康的重要组成部分。