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Abstract
Grant Number: 1R21GM075917-01 Project Title: Structure of- beta barrel membrane protein-lipid bi(RMI)
PI Information: Name Title MARASSI, FRANCESCA M. fmarassi@burnham.org ASSISTANT PROFESSOR Abstract: DESCRIPTION (provided by applicant): The goal of this project is to determine the structure of a beta/b-barrel membrane protein in lipid bilayer membranes, using solid-state NMR spectroscopy. Previous solid-state NMR studies have focused on helical membrane proteins, while the methods for b-barrel sample preparation and structure determination have not been developed. The project is aimed at advancing the current solid-state NMR technology, and has a significant exploratory component. B-barrel membrane proteins, found in the outer membranes of bacteria, chloroplasts and mitochondria, regulate major cellular processes including transport, secretion, adhesion, and apoptosis. Although trans-membrane b-barrels represent approximately 3% of the genomes of gram negative bacteria, and thousands have been identified in the databases, the structures of fewer than 20 unique proteins have been determined, b-barrel membrane proteins have not been previously examined by solid-state NMR in lipid bilayers, and the determination of a structure in its functional environment should provide significant biological insights in health and disease. The structure will also advance the development of solid-state NMR as a method for the structure determination of membrane proteins. The techniques learned while developing the sample preparation methods for b-barrels will also be useful for other membrane proteins, and the availability of another highly-oriented membrane protein sample will serve as a testing ground for the existing methods, and drive new spectroscopic an computational developments. We will focus on the b-barrel membrane protein OmpX from E. coli, and its homolog from Y. pestis. The x- ray and NMR structures of E. coli OmpX have been determined, and will serve as useful comparisons for the structure we determine in lipid bilayers. By the end of this two-year project we expect to have learned to prepare highly oriented samples of OmpX, and to have determined its structure in lipid bilayers.
Public Health Relevance:
This Public Health Relevance is not available.Thesaurus Terms:
bacterial protein, lipid bilayer membrane, membrane protein, protein structure, structural biology
nuclear magnetic resonance spectroscopy
Institution: BURNHAM INSTITUTE FOR MEDICAL RESEARCH LA JOLLA, CA 92037 Fiscal Year: 2005 Department: Project Start: 23-SEP-2005 Project End: 31-JUL-2007 ICD: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES IRG: ZRG1