Proposal for an Administrative Supplement for Equipment Purchases for NIGMS Awardees NOT-GM-22-017
Document text
Principal Investigator: Youzhong Guo Organization: VIRGINIA COMMONWEALTH UNIVERSITY Fiscal Year: 2022 Award: $236,127 Funding agency: National Institute of General Medical Sciences Project Summary for Parent Grant R01GM132329 Membrane proteins are essential in living organisms. Protein-lipid interactions are critical for membrane protein structural and functional integrity. High-resolution membrane protein structures are in high demand for understanding their biology and drug development based on structure. Extraction of membrane proteins from cell membranes is frequently required for biochemical and biophysical research. Currently, detergents are the most often used method for extracting membrane proteins. Detergents have several downsides, including the destruction of lipid bilayers and the removal of essential lipid molecules from membrane proteins. We are creating a detergent-free native cell membrane nanoparticles technology for membrane protein research. The native cell membrane nanoparticles system is made up of three parts: 1) Polymers that are membrane-active. 2) Methods for creating native cell membrane nanoparticles. 3) Cryo-EM single particle investigation of native cell membrane nanoparticles. We suggest creating a system that is applicable to both bacterial and eukaryotic membrane proteins. Specific Aim 1 focuses on building techniques to create native cell membrane nanoparticles utilizing our chosen model membrane proteins and constructing a membrane-active polymer library. We have created four prototype membrane active polymers; we intend to expand the active membrane polymers utilizing both commercially available styrene-maleic anhydride copolymers and polymers made in laboratories using similar procedures. Specific Ami 2 focuses on creating procedures for determining the high-resolution structure of selected bacterial model membrane proteins. The third specific aim is to create procedures for high-resolution structures of selected eukaryotic model membrane proteins. The proposed study is interesting because it offers a novel detergent-free method for investigating membrane proteins in their native lipid context. As our first data show, structural knowledge of protein-lipid interactions for membrane proteins is critical for understanding the structure and function of membrane proteins. This approach has the potential to revolutionize the area of membrane protein research and have a significant impact on membrane protein structure-based medication discovery and development. Terms: <Abscission><Administrative Supplement><Area><Bacterial Model><Biochemical><Biology><Biophysics><Cell Membrane Proteins><Cell membrane><Cryo-electron Microscopy><Cryoelectron Microscopy><Cytoplasmic Membrane><Data><Detergents><Development><Drugs><Electron Cryomicroscopy><Excision><Extirpation><Investigation><Knowledge><Laboratories><Libraries><Lipid Bilayers><Lipids><Maleic Anhydride><Medication><Membrane><Membrane Protein Gene><Membrane Proteins><Membrane Structure and Function><Membrane-Associated Proteins><Methods><NIGMS><National Institute of General Medical Sciences><Organism><Pharmaceutic Preparations><Pharmaceutical Preparations><Plasma Membrane><Polymers><Procedures><Proteins><Removal><Research><Resolution><Structure><Styrenes><Surface Proteins><Surgical Removal><System><Techniques><Technology><base><biophysical foundation><biophysical principles><biophysical sciences><copolymer><cryo-EM><cryoEM><developmental><drug development><drug/agent><equipment acquirement><equipment acquisition><equipment investment><equipment procurement><equipment purchase><equipment purchasing><instrument acquisition><instrument investment><instrument procurement><instrument purchase><lipid bilayer membrane><living system><membrane model><membrane structure><nano particle><nano-sized particle><nanoparticle><nanosized particle><novel><parent grant><particle><plasmalemma><protein structure><protein structures><proteins structure><prototype><resection>