Komives, Elizabeth
Structure, function, dynamics and thermodynamics of protein-protein interactions: NMR, mass spectrometry and kinetics

Contact Information
Professor of Chemistry and Biochemistry
Bruno Zimm Scholar

Office: Natural Sciences Bldg 4318
Phone: 858-534-3058
Email: ekomives@ucsd.edu
Web: komiveslab.ucsd.edu
Group: View group members
Education
1987 Ph.D., UC San Francisco
1982 MS, Massachusetts Institute of Technology
1982 BS, Massachusetts Institute of Technology
Awards and Academic Honors
2000
Kaiser Award for Excellence in Teaching
2000
Barany Award for Contributions to Biophysics
1992-1995
Searle Scholar
1991-1996
Rita Allen Scholar
1987-1990
N.I.H. Postdoctoral Fellow, Harvard University
Research Interests
The long-term goal of research in the Komives lab is to understand the parameters that govern protein-protein recognition and the mechanisms by which these interactions contribute to biological function. The relative importance of factors such as hydrophobic effects, electrostatic interactions and dynamics are being defined for several different interactions. These parameters are explored by a combination of molecular biological techniques, protein chemistry, surface plasmon resonance, multidimensional NMR, and mass spectrometry. One project aims to discover how thrombomodulin (TM) converts the pro-coagulant activity of thrombin to anti-coagulant activity. The thrombin-TM interaction involves diffusion-controlled association that is highly electrostatically steered. The binding has no favorable enthalpy change, but is instead driven by entropy. In collaboration with the McCammon group, we have obtained evidence from Accelerated Molecular Dynamics that the TM binding site is dynamically coupled to motions at the thrombin active site. We recently were able to obtain beautiful NMR spectra for thrombin, and are now characterizing its dynamics.

A second project in the lab is a joint effort with the G. Ghosh, A. Hoffmann, P. Wolynes and J. Dyson labs. This involves understanding the signal transduction mediated by the family of NFkB transcription factors and their IkB inhibitors. We determined that the binding energy of the complex between IkBa and NFkB (p50/p65) lies at the ends of the binding interface. We showed that IkBa folds upon binding to NFkB and that the fifth and sixth ankyrin repeats are weakly folded according to amide exchange experiments. The weakly-folded parts of IkBa appear to be important for facilitating removal of NFkB from transcription sites and we showed by single molecule FRET that they slowly fluctuate between folded and unfolded states. Taking off on this project, we are now investigating other protein-protein interactions mediated by ankyrin-repeat domain proteins. In particular, we are studying the interaction between ASB9, one member of a large family of E3 ubiquitin ligases, and its target, Creatine Kinase.

A third project in the lab is to develop novel proteases for proteomics applications. Starting from alphalytic protease, a particularly stable and highly active protease, we are evolving a family of proteases with unique substrate specificity to expand the protein sequence coverage in proteomics experiments.
Primary Research Area
Biochemistry
Interdisciplinary interests
Biophysics
Macromolecular Structure

Outreach Activities
Minority Access to Careers committee member, Biophysical Society (helped develop summer course in Biophysics for underrepresented students that was recently funded by the NIH)

Diversity Coordinator Department of Chemistry and Biochemistry

Steering Committee member in charge of recruitment of underrepresented students for Molecular Biophysics Training Program

Ph. D. thesis advisor for several underrepresented minorities.

Mentor for underrepresented minority undergraduates and postdoctoral scholars.

Hosted Preuss School students in lab for Science Fair Projects

Founding Faculty of Academic Connections Research Scholars Program – this program brings 15-20 high school students to UCSD for 3 weeks to work in a research lab.
Image Gallery


Ensemble of thrombin structures that best represents the NMR-derived residual dipolar couplings

Single molecule FRET traces showing the fluctuations within the IkBa molecule

Selected Publications