- Graduate Education
- Ph.D. Columbia University, 2003
- Postdoc. University of Pennsylvania, 2003-2005
- Postdoc. Columbia University, 2005-2007
- Joined Texas A&M in 2008
- NSF CAREER Award 2012
- Ralph E. Powe Junior Faculty Award 2010
Structural biology of peripheral membrane proteins involved in signal transduction
My laboratory is broadly interested in understanding the structural basis of signal transduction events that occur at the membrane surface. These events are mediated by signaling proteins that reversibly associate with membranes in response to binding second messengers, such as Ca2+ ions, diacylglycerol, and phosphoinositides. One of the key kinases regulating these signal transduction pathways is the Protein Kinase C (PKC) family. Aberrant levels of PKC expression or activity have been implicated in a large number of human diseases, such as cancer, cardiac failure, Alzheimer’s disease, and diabetes. Despite the significance of PKC in signal transduction and human health, the structural and dynamical basis of its activation upon binding to lipid membranes remains elusive.
The ultimate objective of our studies is to understand how PKCs function at the atomic level. Our experimental approach is multi-faceted. We primarily rely on advanced Nuclear Magnetic Resonance (NMR) spectroscopy techniques, but also use fluorescence spectroscopy, X-ray crystallography, and computational methods to gain insight into various aspects of structure, dynamics, and function of PKC. We anticipate that our studies will inform and facilitate the design of agents that modulate the PKC activity for both therapeutic and research purposes. A related area of interest is the fundamental biophysics of peripheral lipid-binding domains that target their host proteins to membranes.
Katti, S, Nyenhuis, SB, Her, B, Srivastava, AK, Taylor, AB, Hart, PJ et al.. Non-Native Metal Ion Reveals the Role of Electrostatics in Synaptotagmin 1-Membrane Interactions. Biochemistry. 2017;56 (25):3283-3295.
Stewart, MD, Igumenova, TI. Toggling of Diacylglycerol Affinity Correlates with Conformational Plasticity in C1 Domains. Biochemistry. 2017;56 (21):2637-2640.
Morales, KA, Yang, Y, Cole, TR, Igumenova, TI. Dynamic Response of the C2 Domain of Protein Kinase Cα to Ca(2+) Binding. Biophys. J. 2016;111 (8):1655-1667.
Igumenova, TI. Dynamics and Membrane Interactions of Protein Kinase C. Biochemistry. 2015;54 (32):4953-68.
Ghosh, R, de Campos, MK, Huang, J, Huh, SK, Orlowski, A, Yang, Y et al.. Sec14-nodulin proteins and the patterning of phosphoinositide landmarks for developmental control of membrane morphogenesis. Mol. Biol. Cell. 2015;26 (9):1764-81.
Cole, TR, Igumenova, TI. Expression and purification of the N-terminal regulatory domain of Protein Kinase C for biophysical studies. Protein Expr. Purif. 2015;110 :14-21.
Stewart, MD, Cole, TR, Igumenova, TI. Interfacial partitioning of a loop hinge residue contributes to diacylglycerol affinity of conserved region 1 domains. J. Biol. Chem. 2014;289 (40):27653-64.
Morales, KA, Yang, Y, Long, Z, Li, P, Taylor, AB, Hart, PJ et al.. Cd2+ as a Ca2+ surrogate in protein-membrane interactions: isostructural but not isofunctional. J. Am. Chem. Soc. 2013;135 (35):12980-3.
Yang, Y, Igumenova, TI. The C-terminal V5 domain of Protein Kinase Cα is intrinsically disordered, with propensity to associate with a membrane mimetic. PLoS ONE. 2013;8 (6):e65699.
Stewart, MD, Igumenova, TI. Reactive cysteine in the structural Zn(2+) site of the C1B domain from PKCα. Biochemistry. 2012;51 (37):7263-77.