Diphtheria Toxin

I worked on dimeric and monomeric Diphtheria toxin (DT) as a graduate student in David Eisenberg's lab at UCLA. Diphtheria toxin is secreted by a bacterium, and kills cells by a 3 step mechanism. The structure of dimeric DT was determined by Senyon Choe in 1992, and revealed that each function is performed by a different domain in the protein. The R domain binds cell-surface receptors, the T domain inserts into endosomal membranes and the C domain is translocated into the cytoplasm, where it inactivates EF-2. I determined the structure of monomeric DT and refined the dimeric DT structure. The comparison of these two structures revealed that the monomer within dimeric DT is "open", which may be involved in membrane insertion.

The "open" monomer

Dimeric DT (left) and monomeric DT (right)

DT publications

• "A structure-based model of diphtheria toxin action"; Eisenberg, D., Bell, C.E., Bennett, M.J., Collier, R.J., Schlunegger, M.P., Steere, B.A. and Weiss, M.S. (1997) in Protein Toxin Structure, edited by Michael W. Parker, R. G. Landes Company

• "Refined structure of monomeric diphtheria toxin at 2.3 Å resolution"; Bennett, M.J. and Eisenberg, D., Protein Science 3, 1464-1475 (1994).

• "Refined structure of dimeric diphtheria toxin at 2.0 Å resolution"; Bennett, M.J. and Eisenberg, D., Protein Science 3, 1444-1463 (1994).

• "Three domains for three functions: The crystal structure of diphtheria toxin"; Choe, S., Bennett, M.J., Fujii, G., Curmi, P., Kantardjieff, K.A., Collier, J.R. and Eisenberg, D., Nature 357, 216-222 (1992).

• "Crystallization of diphtheria toxin"; Fujii, G., Choe, S., Bennett, M.J. and Eisenberg, D., J. Mol. Biol. 222, 861-864 (1991).