Alan Finkelstein

Physiology & Biophysics

Professor
Protein translocation associated with the voltage gating of diphtheria toxin, anthrax toxin, and colicin Ia channels.

Ullmann
Room 205

 

For the past several years we have been studying the voltage-dependent channels formed in planar phospholipid bilayer membranes by diphtheria toxin, colicin Ia and anthrax toxin. The remarkable finding we have discovered with the former two channels is that in association with their opening and closing there is a massive translocation of material back and forth across the membrane. In the case of diphtheria toxin, this consists of the N-terminal 270 residues, and in the case of colicin Ia, a region of at least 70 residues. Moreover, we have shown with the colicin that foreign epitopes inserted in this region are also translocated. Thus these molecules appear to be capable of translocating "any" sequence of polar residues. Our research is directed at deducing the channel structure, identifying the voltage sensor, and determining the mechanism and pathway of protein translocation.

 

Selected Publications

Senzel, L., Huynh, P.D. Jakes, K.S., Collier, R.J., and Finkelstein, A. (1998). The diphtheria toxin channel-forming T-domain translocates its own NH2-terminal region across planar bilayers. J. Gen. Physiol. 112: 317-324.

Oh, K.J., Senzel, L., Collier, R.J., and Finkelstein, A. (1999). Translocation of the catalytic domain of diphtheria toxin across planar phospholipid bilayers by its own T- domain. Proc. Natl. Acad. Sci. 96: 8467-8470.

Jakes, K.S., Kienker, P.K., and Finkelstein, A. (1999). Channel-forming colicins: Translocation (and other deviant behavior) associated with colicin Ia channel gating. Quarterly Rev. Biophys. 32: 189-205.

Senzel, L., Gordon, M., Blaustein, R.O., Oh, K.J., Collier, R.J. and Finkelstein, A. (2000). Topography of diphtheria toxin's T domain in the open channel state. J. Gen. Physiol. 115: 421 434.

Kienker, P.K., Jakes, K.S. and Finkelstein, A. (2000). Protein translocation across planar bilayers by the colicin Ia channel-forming domain: Where will it end? J. Gen. Physiol. 116: 587-597.

Gordon, M. and Finkelstein, A. (2001). The number of subunits comprising the channel formed by the T domain of diphtheria toxin. J. Gen. Physiol. 118: 471-480.

Nassi, S., Collier, R.J. and Finkelstein, A. (2002). PA63 Channel of Anthrax Toxin: An Extended beta-Barrel. Biochemistry 41: 1445-1450.

Kienker, P.K., Jakes, K.S., Blaustein, R.O., Miller, C. and Finkelstein, A. (2003). Sizing the protein translocation pathway of colicin Ia channels. J. Gen. Physiol. 122: 161-176.