|Professor Pletneva received her undergraduate education and M.S. degree in Chemistry from the Higher Chemical College of the Russian Academy of Sciences. She obtained her Ph.D. in Inorganic Chemistry in 2001 from Iowa State University. After postdoctoral studies with Professor Amy H. Andreotti at Iowa State University and Professor Harry B. Gray at the California Institute of Technology, she joined the faculty of Dartmouth College in the summer of 2007. Among other honors, Professor Pletneva is the recipient of the Dartmouth College Class of 1962 Faculty Award for Outstanding Teaching and the 2010 NSF CAREER Award.|
Position: Assistant Professor of Chemistry
E-Mail: Ekaterina V. Pletneva
Nature has designed a clever mechanism for biological information transfer – highly dynamic proteins that switch their conformations and activity in response to signaling inputs (Figure 1). The protein redox activity is often affected by such ‘switching’ and the redox reactions themselves can sometimes act as triggers of protein rearrangements. However, mechanisms of redox-linked conformational changes are poorly understood. Understanding the mechanistic principles of these changes could provide valuable insights for the design of conformational drugs as well as switchable components for molecular electronics and artificial photosynthesis.
Our studies examine the interplay between protein dynamics and redox reactivity in signaling transformations and address fundamental problems in reaction mechanisms, coordination chemistry and biology. We focus primarily on bioinorganic systems where intrinsic or engineered metal sites provide access to unique chemistry and rich spectroscopy. We employ a wide range of experimental approaches including development and synthesis of new protein dynamics probes, mutational analysis in vitro and in vivo, and time-resolved optical spectroscopy. Powerful measurements of electron- and energy-transfer kinetics allow us to observe and quantitatively characterize conformational transitions, determine structural changes and corresponding energy barriers, as well as evaluate composition of heterogeneous ensembles. As these experiments map the entire energy landscapes of protein folding and function, they provide a detailed framework for understanding signaling transformations and redox reactivity.
Heme signaling proteins are the main subjects of our research. We are investigating conformational properties of cytochrome c in apoptosis and correlate them to the protein peroxidase activity, which is critical for execution of this cellular pathway. We are also studying redox reactivity and folding of a group of sensor proteins, in which changes in the oxidation state of the heme are linked to heme ligand substitution resulting in protein conformational rearrangements. With mutations and kinetic experiments, we are identifying the key components of these redox-linked biological switches.
Figure 1. Conformational switching and functional activity of proteins.
• A. J. Vincelli, D. S. Pottinger, F. Zhong, J. Hanske, S. G. Rolland, B. Conradt, E. V. Pletneva "Recombinant expression, biophysical characterization, and cardiolipin-induced changes of two Caenorhabditis elegans cytochrome c proteins", Biochemistry 2013, in press.
• Y. Hong, J. Muenzner, S. K. Grimm, E. V. Pletneva "Origin of the conformational heterogeneity of cardiolipin-bound cytochrome c", J. Am. Chem. Soc. 2012, 134, 18713–18723.
• T. L. Freeman, Y. Hong, K. H. Schiavoni, D. M. I. Bandara, E. V. Pletneva "Changes in the heme ligation during folding of a Geobacter sulfurreducens sensor GSU0935" Dalton Transactions 2012, 41, 8022-8030.
• J. Hanske, J. R. Toffey, A. M. Morenz, A. J. Bonilla, K. H. Schiavoni, E. V. Pletneva "Conformational properties of cardiolipin-bound cytochrome c" Proc. Nat. Acad. Sci. 2012, 109, 125-130.
• G. J. Pound, A. A. Pletnev, X. Fang, and E. V. Pletneva "A small fluorophore reporter of protein conformation and redox state" Chem. Commun. 2011, 47, 5714-5716.
• J. L. Taylor, T. G. Moga, O. Karagiaridi, D. E. Wilcox, and E. V. Pletneva "Effects of DNA binding on the structural and redox properties of the [2Fe-2S] transcription factor SoxR" Chemtracts – Inorganic Chemistry, 2008, 21, 336-345.
Last Updated: 1/3/13