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Dr. Englander's laboratory is interested in macromolecular structure, dynamics, and function and has developed the use of hydrogen exchange (HX) approaches in protein and nucleic acid studies. Many hydrogens in proteins and nucleic acids are in continual exchange with the hydrogens in solvent water. These can provide literally hundreds of probe points that are sensitive to structure, structure change, internal dynamics, energy, and functional interactions at identifiable positions throughout a macromolecule. Work in this lab has explained the chemistry of protein and nucleic acid HX processes and has formulated the physical models that appear to explain the ways in which internal motions in proteins and nucleic acids determine the HX rates of their individual protons. The lab has developed and is using special hydrogen exchange methods that can measure the specific parts of any protein involved in any function, the protein folding process as it occurs on a sub-second time scale, the energetic stability of individual bonding interactions, structure change, etc. Methods in use include the range of protein biophysical techniques including 2D NMR, mass spectrometry, fast reaction stopped-flow, spectroscopy, and mutational analysis. The lab has in recent years produced a coherent explanation for how proteins fold, and discovered the new foldon dimension of protein structure and behavior. Present work is directed at testing and enlarging the folding model and investigating the broader significant of the foldon paradigm.
Selected Publications: Lim, W.K., Rösgen, J., Englander, S. W. (2008) Urea, but not guanidinium, destabilizes proteins by forming hydrogen bonds to the peptide group. Proc. Natl. Acad. Sci. USA 106:2595-2600. Skinner, J.J., Wood, S., Shorter, J., Englander, S.W., Black, B.E. (2008) The Mad2 partial unfolding model: Regulating mitosis through Mad2 conformational switching. J. Cell Biol. 183:761-768. Bédard, S., Krishna, M. M. G., Mayne. L, Englander, S. W. (2008) Protein folding: Independent unrelated pathways or predetermined pathway with optional errors. Proc. Natl. Acad. Sci. USA 105:7182 – 7187. Englander, S.W., Mayne, L., Krishna, M.M.G. (2008) Protein folding and misfolding: mechanism and principles. Q. Rev. Biophys. 40:287-326. Bédard, S., Mayne, L. C., Peterson, R. W., Wand, A. J., Englander, S. W. (2007) The foldon substructure of staphylococcal nuclease. J. Mol. Biol. 376:1142 –1154. Horst, R., Fenton, W. A., Englander, S. W., Wüthrich, K., Horwich, A. L. (2007) Folding trajectories of human dihydrofolate reductase inside the GroEL GroES chaperonin cavity and free in solution. Proc. Natl. Acad. Sci. USA 104:20788-20792. Krishna, M. M. G., Maity, H., Rumbley, & Englander, S. W. (2007) Branching in the sequential folding pathway of cytochrome c. Protein Sci. 16:1-11. Krishna, M.M.G., Englander, S. W. (2007) A unified mechanism for protein folding. Predetermined pathways with optional errors. Protein Sci. 16:449-464. |
