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PEPTIDE/LIPID STUDIES IN FIELD ORIENTED MEMBRANES

场定向膜中的肽/脂质研究

基本信息

批准号：
2605380
负责人：
KATHLEEN P HOWARD
金额：
$ 10.5万
依托单位：
SWARTHMORE COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
1998
资助国家：
美国
起止时间：
1998-05-01 至 2002-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2605380
关键词：
electron spin resonance spectroscopy lipid bilayer membrane magnetic field membrane lipids membrane proteins membrane structure method development nuclear magnetic resonance spectroscopy

项目摘要

DESCRIPTION (Adapted from applicant's abstract): Despite the abundance and clear importance of membrane-bound molecules, there is a dramatic lack of high resolution structural data on membrane systems. The overall goals of this research are the development and testing of new methodology that is capable of providing atomic level structural and dynamic information on membrane-bound proteins in a lipid bilayer. The methods utilize phospholipid bilayer arrays that spontaneously orient in magnetic fields and allow for high resolution spectroscopy in a model for a natural membrane. These methods will be applied to model transmembrane helical peptides: one of the fundamental structural motifs found in membrane proteins. Transmembrane helices have been shown to have many important functions, including defining channels and transport pathways, positioning prosthetic groups for electron transfer reactions, and mediating transmembrane signaling. The first step in the study will be to optimize the magnetic field orientable lipid bilayers for novel nuclear magnetic resonance (NMR) studies of transmembrane peptides. Next, the order and orientation of specific peptides in a model membrane helix will be determined using 2H NMR spectroscopy. Finally, information about the interaction of the transmembrane peptides with the surrounding lipid bilayer will be measured using both oriented 2H NMR and novel oriented electron spin resonance (ESR) experiments. Investigations of prototypal transmembrane helices will not only help establish the feasibility of the magnetic orientation methodology, but will also answer some of the basic questions that surround the properties of transmembrane helices, as well as their interactions with lipid bilayers. Although the studies proposed here are for single transmembrane helices, this work will pave the way for studies of larger fragments and intact membrane proteins.

描述（改编自申请人的摘要）：尽管丰富和虽然膜结合分子的重要性很明显，但严重缺乏膜系统的高分辨率结构数据。的总目标这项研究是开发和测试新的方法，能够提供原子级结构和动态信息，脂质双层中的膜结合蛋白质。述方法使用磷脂双层阵列在磁场中自发取向，允许在天然膜的模型中进行高分辨率光谱分析。这些方法将应用于跨膜螺旋肽的建模：膜蛋白的基本结构基序。跨膜螺旋已被证明具有许多重要的功能，包括确定通道和运输途径，定位假体基团的电子转移反应，并介导跨膜发信号。研究的第一步将是优化磁场用于新型核磁共振（NMR）研究的可定向脂质双层跨膜肽。接下来，具体的顺序和方向将使用2H NMR测定模型膜螺旋中的肽谱最后，关于将测量具有周围脂质双层的跨膜肽使用定向2H NMR和新型定向电子自旋共振（ESR）实验对原型跨膜螺旋的研究不仅有助于建立磁取向方法的可行性，但将还回答了一些基本的问题，围绕的性质，跨膜螺旋，以及它们与脂质双层的相互作用。虽然这里提出的研究是针对单跨膜螺旋，这项工作将为研究更大的碎片和完整的膜蛋白