Komives, Elizabeth
Structure, function, dynamics and thermodynamics of protein-protein interactions: NMR, mass spectrometry and kinetics
Education
1987 Ph.D.,
UC San Francisco
1982 MS,
Massachusetts Institute of Technology
1982 BS,
Massachusetts Institute of Technology
Awards and Academic Honors
2023
Fellow of the American Association for the Advancement of Science
2010
Bruno Zimm Scholar
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 Komives lab pioneered using hydrogen deuterium exchange to map protein-protein interfaces by HDX-MS. Combining HDX-MS with NMR and single molecule FRET allowed them to address important but unsolved questions about allosteric regulation of proteins. Initial discoveries focused on the biophysical behavior of thrombin:thrombomodulin complexes. They discovered that thrombomodulin alters the dynamic ensemble of thrombin to favor the catalytically active state. It furthermore induces motions on multiple timescales linked to catalysis. Work on NFB-IB signaling established an original paradigm demonstrating kinetic control of transcription factor dynamics. Here, single molecule FRET was used to demonstrate slow timescale motions that expose the IκBα degron and that expose NFκB to facilitated dissociation from the DNA mediated by IκBα. In another project, we uncovered allostery through a 10-protein ubiquitin E3 ligase complex. In this complex, an ankyrin repeat protein and Cullin 5 each act as a rigid rod connecting the substrate binding site to the ubiquitylation machinery. The lab utilizes a broad range of biophysical tools to discover new principles, which have profoundly advanced our fundamental understanding of macromolecular recognition.
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
- Komives EA "Dynamic allostery in thrombin-a review.", Front Mol Biosci, 2023, Vol. 10, 1200465
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- Torres-Paris C,Chen Y,Xiao L,Song HJ,Chen P,Komives EA "The autoactivation of human single-chain urokinase-type plasminogen activator (uPA).", J Biol Chem, 2023, Vol. 299, Issue 10, 105179
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- Baughman HER,Narang D,Chen W,Villagrán Suárez AC,Lee J,Bachochin MJ,Gunther TR,Wolynes PG,Komives EA "An intrinsically disordered transcription activation domain increases the DNA binding affinity and reduces the specificity of NFκB p50/RelA.", J Biol Chem, 2022, Vol. 298, Issue 9, 102349
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- Peacock RB,McGrann T,Zaragoza S,Komives EA "How Thrombomodulin Enables W215A/E217A Thrombin to Cleave Protein C but Not Fibrinogen.", Biochemistry, 2022, Vol. 61, Issue 2, 77-84
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- Chen W,Lu W,Wolynes PG,Komives EA "Single-molecule conformational dynamics of a transcription factor reveals a continuum of binding modes controlling association and dissociation.", Nucleic Acids Res, 2021, Vol. 49, Issue 19, 11211-11223
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- Lumpkin RJ,Ahmad AS,Blake R,Condon CJ,Komives EA "The Mechanism of NEDD8 Activation of CUL5 Ubiquitin E3 Ligases.", Mol Cell Proteomics, 2021, Vol. 20, 100019
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- Peacock RB,Komives EA "Hydrogen/Deuterium Exchange and Nuclear Magnetic Resonance Spectroscopy Reveal Dynamic Allostery on Multiple Time Scales in the Serine Protease Thrombin.", Biochemistry, 2021, Vol. 60, Issue 46, 3441-3448
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- Peacock RB,McGrann T,Tonelli M,Komives EA "Serine protease dynamics revealed by NMR analysis of the thrombin-thrombomodulin complex.", Sci Rep, 2021, Vol. 11, Issue 1, 9354
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- Lumpkin RJ,Baker RW,Leschziner AE,Komives EA "Structure and dynamics of the ASB9 CUL-RING E3 Ligase.", Nat Commun, 2020, Vol. 11, Issue 1, 2866
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- Kopcho N,Chang G,Komives EA "Dynamics of ABC Transporter P-glycoprotein in Three Conformational States.", Sci Rep, 2019, Vol. 9, Issue 1, 15092
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