photo by Will Kirk/JHU

Professor
Department of Materials Science and Engineering
Whiting School of Engineering

hristova@jhu.edu

102 Maryland Hall
3400 N. Charles Street
Baltimore, MD 21218

Office: 410-516-8939
Lab: 410-516-7142

Membranes and membrane proteins are abundant in eukaryotic cells. About 30% of all human proteins are expected to be membrane-associated. The pharmacological importance of membrane proteins is determined by the role they play in vital processes such as cell adhesion, recognition, motility, proliferation, energy production, transport of nutrients and cholesterol, and cell signaling. Despite their functional importance and abundance, it is not yet clear how the majority of these proteins function at the molecular level, and how the membrane shapes protein function.

We use diverse biophysical and cell biological methods such as X-ray and neutron diffraction, fluorescence, Western blotting, circular dichroism, equilibrium dialysis, and molecular modeling to address questions such as:

• What structural and thermodynamic laws govern membrane protein folding (and pathogenic misfolding)?
• How do mutations in the transmembrane segments of catalytic receptors induce pathological phenotypes such as cancers and growth disorders?
• Can we, through structural and kinetic studies of membrane proteins, arrive at a “recipe” for the rational design of drugs that inhibit persistent membrane protein activation?
• How does the lipid bilayer mediate protein-protein interactions?
  

Selected Publications

He, L., and K. Hristova. (2011) Physical-chemical principles underlying RTK activation, and their implications for human disease. Biochim. Biophys. Acta- Biomembranes (in press)

Li, E., W.C. Wimley, and K. Hristova. (2011) Transmembrane helix dimerization: Beyond the search for sequencxe motifs. Biochim. Biophys. Acta- Biomembranes (in press)

Chen, F., and K. Hristova. (2011) The physical basis of FGFR3 response to fgf1 and fgf2. Biochemistry (in press)

He, L., A. Hoffmann, C. Serrano, K. Hristova, and W.C. Wimley. (2011) High-throughput selection of transmembrane sequences that enhance receptor tyrosince kinase activation. J. Mol. Biol. 412:43-54.

Marks, J., J. Placone, K. Hristova, and W.C. Wimley. (2011) Spontaneous membrane-translocating peptides by orthogonal high-throughput screening. J. Am. Chem. Soc. 133:8995-9004.

Chen, F., C. Degnin, M. Laedrich, W.A. Horton, and K. Hristova. (2011) The A391E mutation enhances FGFR3 activation in the absence of ligand. Biochim. Biophys. Acta- Biomembranes 1808:2045-2050.

He, L., N. Shobnam, W.C. Wimley, and K. Hristova. (2011) FGFR3 heterodimerization in achondroplasia, the most common form of human dwarfism. J. Biol. Chem. 286:13272-13281.

Wimley, W.C., and K. Hristova. (2011) Antimicrobial peptides: Successes, challenges, and unanswered questions. J. Membr. Biol. 239:27-34.

Hristova, K., and W.C. Wimley. (2011) A look at arginine in membranes. J. Membr. Biol. 239:49-56.

He, L., N. Shobnam, and K. Hristova. (2011) Specific inhibition of a pathogenic receptor tyrosine kinase by its transmembrane domain. Biochim. Biophys. Acta- Biomembranes 1808:253-259.

He, L., W. Horton, and K. Hristova. (2010) The physical basis behind achondroplasia, the most common form of human dwarfism. J. Biol. Chem. 285:30103-30114.

Chen, L., J. Placone, L. Novicky, and K. Hristova. (2010) The extracellular domain of fibroblast growth factor receptor 3 inhibits ligand-independent dimerization. Science Signaling 3:ra86.

Chen, L., L. Novicky, M. Merzlyakov, T. Hristov, and K. Hristova. (2010) Measuring the energetics of membrane protein dimerization in mammalian membranes. J. Am. Chem. Soc. 132:3628-3635.

Lin, J., J. Szymanski, P. Searson, and K. Hristova. (2010) Electrically addressable, biologically relevant surface supported bilayers. Langmuir 26:3544-3548.

Li, E., and K. Hristova. (2010) Receptor Tyrosine Kinase transmembrane domains: function, dimer structure, and dimerization energetics. Cell Adh. Migr. 4:249-254.

Lin, J., J. Szymanski, P. Searson, and K. Hristova. (2010) Effect of a polymer cushion on the electrical properties and stability of surface-supported lipid bilayers. Langmuir 26:3544-3548.

Snider, C., S. Jayasinghe, K. Hristova, and S.H. White. (2009) MPEx: a tool for exploring membrane proteins. Protein Sci. 18:2624-2628.

Chen, L., M. Merzyakov, Tomer Cohen, Yechiel Shai, and K. Hristova. (2009) Energetics of ErbB1 transmembrane domain dimerization in lipid bilayers. Biophys. J. 96:4622-4630.

Li, E., M. Merzyakov, J. Lin, P. S. Searson, and K. Hristova. Utility of surface supported bilayers in studies of transmembrane helix dimerization. (2009) J. Struct. Biol. 168:53-60.

Soong, R., M. Merzlyakov, L., and K. Hristova. (2009) Hill coefficient analysis of transmembrane helix dimerization. J. Membr. Biol. 230:49-55.

Han, X., and K. Hristova. (2009) Viewing the bilayer hydrocarbon core using neutron diffraction. J. Membr. Biol. 227:123-131.

Walkenhorst, W., M. Merzyakov, K. Hristova, and W.C. Wimley. (2009) Polar residues in transmembrane helices can decrease electrophoretic mobility in polyacrylamide gels without causing helix dimerization. BBA-Biomembranes 1788:1321-1331.

O'Connor, S., E. Li, B.S. Majors, L. He, J. Placone, D. Baycin, M. Betenbaugh, and K. Hristova. (2009) Increased expression of the integral membrane protein ErbB2 in Chinese hamster ovary cells expressing the anti-apoptotic gene Bcl-xL. Protein Expr. Purif. 67:41-47.

Merzyakov, M., E. Li, and K. Hristova. (2009) A surface supported bilayer platform for studies of lateral association of proteins in membranes. Biointerphases 3:FA80-FA84.

He, L., and K. Hristova. (2008) Pathogenic activation of receptor tyrosine kinases in cellular membranes. J. Mol. Biol. 384:1130-1142.

Chang, W.K., W.C. Wimley, P.S. Searson, K. Hristova, and M. Merzyakov. (2008) Characterization of antimicrobial peptide activity by electrochemical impedance spectroscopy. BBA-Biomembranes 1778:2430-2436.

Li, E., J. Placone, M. Merzyakov, and K. Hristova. (2008) Quantitative measurements of protein interactions in a crowded cellular environment. Anal. Chem. 80:5976-5985.

Posokhov, Y.O., M. Merzyakov, K. Hristova, and A.S. Ladokhin. (2008) A simple “proximity” correction for FRET efficiency determination in membranes using lifetime measurements. Anal. Biochem. 380:134-136.

Han, X., K. Hristova, and W.C. Wimley. (2008) Protein folding In membranes: insights from neutron diffraction studies of a membrane beta-sheet oligomer. Biophys. J. 94:492-505.