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Patricia Jennings
Biophysical chemistry: protein structure, dynamics and folding; 2, 3 and 4D NMR spectroscopy; PCR; equilibrium and kinetic-fluorescence, absorbance and circular dichroism spectroscopies |
| Contact Information |
| Office: NSB 3111 |
| Phone: (858) 534-6417 |
| Fax: (858) 534-7042 |
| Email: pajennings@ucsd.edu |
| View group members
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| Education and Appointments |
| 1991 |
Ph.D., The Pennsylvania State University
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| 1985 |
B.S., Rutgers University
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| Awards and Academic Honors |
| 1997 |
Sloan Research Fellow |
| 1996 |
Hellman Faculty Fellow |
| 1991-1994 |
NIH Postdoctoral Fellow, The Scripps Research Institute |
| Research Interests |
While it is critical for a protein's structure to be unique and stable, changes in this structure are imperative for binding and catalysis. It is now evident that many protein recognition processes incorporate conformational changes as a requisite event for function. In this manner, protein structure and dynamics are intimately linked with biological activity. We utilize a combination of methods including high resolution multinuclear NMR for solution structure determination, and stopped flow optical, hydrogen/deuterium exchange and mass spectrometric techniques to investigate how protein structure and dynamics are linked with biological activity in solution. Specifically, we are asking: (1) The fundamental question of how amino acid sequence directs protein folding and assembly and (2) What protein/protein interactions are responsible for localization and modulation of signal transduction events?
Figure 1 . Three dimensional plot of the relative abundance of the observed species as a function of the mass/charge ratio and folding time prior to application of the labeling pulse. Data spanned folding times of 10 msec to 2 hrs. Mass/charge ratio is plotted rather than molecular weight for improved clarity in the figure.
Protein Folding: We are investigating the folding pathway of Il-1ß with a combination of solvent perturbation, molecular biological and biophysical techniques in our laboratory. Of central importance are the results of our hydrogen-exchange/mass spectrometric analysis studies. The beauty of the pulse-labeling hydrogen exchange and ESI-MS approach to folding kinetics is that ESI-MS allows the direct detection of distinct populations of native, unfolded and intermediate species.
Sturctural Basis for Kinase Anchoring: One of the first identified protein-protein interactions incorporating localization involved the interaction of the cAMP-dependent protein kinase (PKA) with A-Kinase Anchoring Proteins (AKAPs). AKAPs contain multiple binding sites, one that interacts with various isoforms of the regulatory subunit of PKA, a second that targets the AKAP to membranes, structural proteins, or cellular organelles, and in some cases, third and fourth sites which colocalize the Ca2+/phospolipid dependent protein kinase, PKC, and a protein phosphatase along with PKA. Thus localization may afford mechanisms for both specificity in signalling events and integration of diverse signalling pathways. Localization of PKA occurs through interactions of a helical segment on the AKAP with the N-terminal dimerization domain of the type II± regulatory subunit (RII± (1-44)). We initially focused on determining the solution structure of 15N and 13C enriched RII± (1-44) using multidimensional heteronuclear NMR techniques.
Figure 2. Backbone Fold and Protomer Orientation of RII (1-44). (a) Stereoviews of the best fit superposition of the 17 lowest energy structures of RII(1-44) dimer generated in X-PLOR 3.851. The independent protomers are colored in red and blue, respectively. (b) This view highlights the alternate antiparallel packing of helices in the X-type four helix bundle.
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| Primary Research Area: |
Interdisciplinary Specialties: |
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Biochemistry
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Biophysics
Macromolecular Structure
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| Image Gallery: |
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Figure 1: Three dimensional plot of the relative abundance of the observed species as a function of the mass/charge ratio and folding time prior to application of the labeling pulse. Data spanned folding times of 10 msec to 2 hrs. Mass/charge ratio is plotted rath |
Figure 2: Backbone Fold and Protomer Orientation of RII (1-44). (a) Stereoviews of the best fit superposition of the 17 lowest energy structures of RII(1-44) dimer generated in X-PLOR 3.851. The independent protomers are colored in red and blue, respectively. (b) |
| Selected Publications |
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Glycinamide Ribonucleotide Transformylase Undergoes pH-dependent Dimerization. With C. A. Mullen. J. Mol. Biol. 262, 746 (1996).
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Evidence for an Obligatory Intermediate in the Folding of Interleukin-1b. With D.K. Heidary, L.A. Gross, and M. Roy. Nat. Struct. Biol. 4, 1 (1997).
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The Molecular Basis for Protein Kinase A Anchoring Revealed by Solution NMR. With M.G. Newlon, M. Roy, D. Morikis, Z.E. Hausken, V. Coghlan, and J.D. Scott. Nat. Struc. Biol. 6(3), 222 (1999).
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Aggregation Events Occur prior to Stable Intermediate Formation during Refolding of Interleukin-1-beta. With J.M. Finke, M. Roy, and B. Zimm. Biochem. 39 (3), 575 (2000).
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An Essential Intermediate in the Folding of Dihydrofolate Reductase. With D.K. Heidary, J.C.O'Neill Jr., and M. Roy. PNAS. 97, 5866 (2000).
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Commitment to Folded and Aggregated States occurs late in Interleukin-1B Folding. With J.M. Finke, L.A. Gross, H.M. Ho, D. Sept, and B.H. Zimm. Biochemistry. 39(50), 15633 (2000).
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