Ultrafast Processing in Proteins and Other Assemblies

蛋白质和其他组装体的超快处理

基本信息

批准号：
7932592
负责人：
ROBIN Main HOCHSTRASSER
金额：
$ 11.53万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-30 至 2010-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7932592
关键词：
Accounting Actins Amides Biological Process Cell Surface Receptors Cell physiology Classification Code Complement Coupled Coupling Deuterium Drug Delivery Systems Elements Equilibrium Evolution Frequencies Genetic Glycophorin A Health 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 Organism Oxidation-Reduction Pathway interactions Peptides Population Process Proline Proteins Research Research Personnel Resolution Robin bird Spectrum Analysis Structure System Temperature Testing Theoretical model Time Translating Transmembrane Domain Work base cytochrome c design dimer 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

Accounting Actins Amides Biological Process Cell Surface Receptors Cell physiology Classification Code Complement Coupled Coupling Deuterium Drug Delivery Systems Elements Equilibrium Evolution Frequencies Genetic Glycophorin A Health 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 Organism Oxidation-Reduction Pathway interactions Peptides Population Process Proline Proteins Research Research Personnel Resolution Robin bird Spectrum Analysis Structure System Temperature Testing Theoretical model Time Translating Transmembrane Domain Work base cytochrome c design dimer 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

展开

项目摘要

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. *

蛋白质结构如何随着跨膜（TM）螺旋的时间变化的残留水平可视化，快速折叠蛋白和二级结构的元素将通过二维红外光谱法找到（2d ir）一种新的，有力的结构生物学方法。肽和蛋白质的同位素标记增强了 2D IR的空间分辨率将其扩展到较大的肽。螺旋螺旋界面涉及的弱键 of TM sections of Glycophorin A will be accessed to obtain the motions of groups in the interface regions and 发现它们如何稳定TM蛋白中的螺旋 - 螺旋相互作用。 2d ir以整个膜的空间布置。疏水作用，极性，氢键和掩埋残留物之间的其他弱相互作用启发了螺旋的机制和结构基础协会。具有多个IR频率的2D IR，访问疏水界面，相关性在不同空间位置的波动与跨膜螺旋中的N-H/N-D交换之间。独立折叠的蛋白质子域是解决折叠问题的重要工具。 2D IR快速非指数文件夹将允许访问二级结构的实时演变，并挑战所有 villin头饰的原子分子动力学来自肌动蛋白捆绑蛋白villin，这与肠道和肾脏上皮。同位素标记的2D IR将访问折叠途径螺旋和疏水核心。氧化还原蛋白中的中间体细胞色素-C将是用新型温度诱导的pH值检查。设计肽的折叠的描述将是 2d IR寻求可视化它们如何组装和加强与理论的关系。研究涉及膜蛋白是细胞生理的重要成分的膜蛋白：它们包括细胞表面受体，离子通道，转运蛋白和氧化还原蛋白。整体膜蛋白占所有四分之一较高生物体中的编码序列，以及所有商业药物的一半以上针对此类蛋白质。尽管如此，对其3D结构及其动态的研究仍然有限。蛋白质折叠是高度相关，因为这是将遗传信息转化为所有人生物学功能的关键步骤类型，因此它的控制是理解人类健康的重要组成部分。 *