Jennings, Patricia
Biophysical chemistry: protein structure, dynamics and folding; 2, 3 and 4D NMR spectroscopy; PCR; equilibrium and kinetic-fluorescence, absorbance and circular dichroism spectroscopies
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
Professor of Chemistry and Biochemistry
Office: Natural Sciences Bldg 3111
Phone: 858-534-6417
Email: pajennings@ucsd.edu
Web: jenningslab.ucsd.edu
Group: View group members
Office: Natural Sciences Bldg 3111
Phone: 858-534-6417
Email: pajennings@ucsd.edu
Web: jenningslab.ucsd.edu
Group: View group members
Education
1991 Ph.D., The Pennsylvania State University
1985 B.A., Rutgers University
1991 Ph.D., The Pennsylvania State University
1985 B.A., Rutgers University
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.
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.
Primary Research Area
Biochemistry
Biochemistry
Interdisciplinary interests
Biophysics
Macromolecular Structure
Macromolecular Structure
Outreach Activities
Mentoring of both underrepresented minorities and women (especially those starting families and also those recovering from domestic abuse situations) for careers in the physical sciences. My laboratory has produced eleven children (and counting). While this may seem irrelevant to some, one of the most common reasons for female scientists to leave the field is because of their inability to find the right balance between career and family needs. Providing a supportive environment while still holding high standards has allowed me to be a successful mentor of talented female and male students who still love science after beginning their families.
Invited to participate in review panel for Minority/Diversity Pre-doctoral Fellowships (NIH), Washington DC
San Diego Science Olympiad Volunteer
Hosted undergraduate interns of CSU-San Marcos “Diversity Initiative Summer Research Program”
Panel Organizer and Participant (Outreach) at NIH Mock Review Panel, Protein Society Symposium, Special Event, in an effort to educate new investigators to the NIH Review Process.
Member- Career and Networking Committee of the Protein Society (CNC)
Advised new faculty members in Grantsmanship
Invited to participate in review panel for Minority/Diversity Pre-doctoral Fellowships (NIH), Washington DC
San Diego Science Olympiad Volunteer
Hosted undergraduate interns of CSU-San Marcos “Diversity Initiative Summer Research Program”
Panel Organizer and Participant (Outreach) at NIH Mock Review Panel, Protein Society Symposium, Special Event, in an effort to educate new investigators to the NIH Review Process.
Member- Career and Networking Committee of the Protein Society (CNC)
Advised new faculty members in Grantsmanship
Image Gallery
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
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)
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
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
- 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).
- 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).
- 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).
- 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).
- 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).
- Glycinamide Ribonucleotide Transformylase Undergoes pH-dependent Dimerization. With C. A. Mullen. J. Mol. Biol. 262, 746 (1996).