CAREER: Elucidation of the Conformation and Dynamics of Membrane Proteins by Solid-State NMR

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Hing, MeiMCB-0093398The broad objective of this research is to elucidate membrane protein structure and dynamicsusing advanced solid-state NMR spectroscopy. Membrane proteins regulate cellular transport andcell signaling, thus they are essential for cell survival. Knowledge of their three-dimensionalstructures is crucial for understanding their functions. Solid-state NMR is a promising method forstudying the molecular structure of membrane proteins in their native environment of lipid bilayers.In this CAREER project, the structure and dynamics of a 22 kDa membrane-bound protein, colicinIa channel domain, will be investigated using NMR techniques suitable for extensively isotopicallylabeled proteins. a-helical and b-sheet segments in colicin will be identified and specific structuralconstraints will be measured using chemical shift anisotropies, correlated dipolar couplings, and 1H-1H internuclear distances. The depth of insertion of the protein into the lipid bilayer will bedetermined by 1H spin diffusion techniques. The dynamics of the colicin backbone and sidechainwill be characterized using anisotropic couplings, lineshapes, and relaxation time constants. Thesestudies should provide insight into the mechanism of conformational changes of colicin Ia and other proteins that refold to accomplish their functions. Related to these research objectives areeducational initiatives to modernize the undergraduate chemistry curriculum. A protein structure module for general chemistry will be designed to integrate research with teaching, and create webpages for undergraduate physical chemistry courses. The participation of women in chemistry will be encouraged by recruiting women summer interns into the laboratory.