Directory: Faculty

Peter F. Flynn

Peter F. Flynn

BIOLOGICAL CHEMISTRY

Assistant Professor

B.S. University of Oregon 1983
Ph.D. University of Washington 1989

Phone:(801) 581-3828

Office: 1104 HEB-N

Email: pfflynn@chem.utah.edu

Research Group

Publications

Research Interests

Our research interests are in the areas of structural biology and biophysics. We are interested in characterizing the function of biologically active macromolecules using a technology-inclusive approach that combines structural studies - primarily using solution NMR - with studies of the biophysical properties of the molecules to elucidate the origins of biological activity. Group projects involve studies of the influence of confinement on the structure and dynamics of proteins and nucleic acid oligonucleotides and the relationships between structure, dynamics, and function in protein-RNA interactions.

Studies of Confinement. The complex function of biologically active macromolecules depends not only on the physiochemical attributes of the molecules themselves, but also on the local environment in which the molecules are active. In contrast to standard in vitro study conditions, the cellular environment is relatively crowded, which has been shown to have important implications for protein folding and stability. Although this basic principle has been appreciated for many years, experimental examination of the influence of confinement on the structure, stability and function of macromolecules has developed slowly. Recently, reverse micelles have emerged as an effective model system for probing the effects of confinement on water and more complex encapsulated systems.

Crystal structure of TRAP

(A) Schematic diagram of AOT and Space filling energy minimized model of AOT. (B) Cut-away diagram of a reverse micelle model; cyan designates water molecules.  (C)  Cut-away diagram of a reverse micelle-protein ternary system with an encapsulated protein.

Our major interest in this research is the study of the effects of confinement on both water and water soluble proteins within reverse micelles.  Our planned efforts emphasize the use of multidimensional multinuclear solution NMR spectroscopy and are divided into four major components, which are 1) development of novel approaches for studying confined water; 2) characterization of reverse micelles containing water and/or proteins; 3) determination of structure and dynamics of proteins in the confined encapsulated state; and 4) comparative studies of encapsulation, macromolecular crowding, and in-cell NMR studies.

Crystal structure of NHPX-RNA complex

Comparison of order parameters (S2) for ubiquitin in free and encapsulated states. S2 ranges from 0 to 1, indicating respectively, no restriction and complete restriction of N-H bond vector motion.  Insert shows low solution S2 values of ubiquitin colored in red.

RNA-Protein Interactions. Interactions between polypeptides and RNA oligomers modulate fundamental biological processes.  Much of the current research in the group involves studies of proteins and RNA oligomers that make up the spliceosome (15.5K-U4SL RNA).  The catalytic activity of the spliceosome is known to arise from a complex orchestration of interactions that occur according to a specific time-order, and we are studying several protein-RNA complexes to elucidate structure and function in this vital eukaryotic process.  Our goal is to provide a structural and dynamical basis for understanding the mechanism by which proteins interact with RNA targets. Approaches include efforts to determine structure and dynamics using solution NMR methods and to characterize the thermodynamics and kinetics of the interactions based on fluorescence, calorimetry and biosensor techniques.

Crystal structure of NHPX-RNA complex

15N-HSQC of 15.5K at 800 MHz in 100 mM NaCl, 100 mM NaPO4, pH 6.0 at 20˚ C shown labeled with assignments.

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