Professor, Department of Physiology & Biophysics
PROTEIN TRANSLOCATION ASSOCIATED WITH CHANNEL GATING
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.
Jakes KS, Finkelstein A. (2010). The colicin Ia receptor, Cir, is also the translocator for colicin Ia. Mol Microbiol.72(5):1171-80.
Udho E, Jakes KS, Buchanan SK, James KJ, Jiang X, Klebba PE, Finkelstein A. (2009). Reconstitution of bacterial outer membrane TonB-dependent transporters in planar lipid bilayer membranes. Proc Natl Acad Sci U S A. 106(51):21990-5.
Basilio D, Juris SJ, Collier RJ, Finkelstein A. (2009). Evidence for a proton-protein symport mechanism in the anthrax toxin channel. J Gen Physiol. 133(3):307-14.
Janowiak BE, Finkelstein A, Collier RJ. (2009). An approach to characterizing single-subunit mutations in multimeric prepores and pores of anthrax protective antigen. Protein Sci. 18(2):348-58.
Finkelstein A. (2009). Proton-coupled protein transport through the anthrax toxin channel. Philos Trans R Soc Lond B Biol Sci. 364(1514):209-15.
Kienker PK, Jakes KS, Finkelstein A. (2008). Identification of channel-lining amino acid residues in the hydrophobic segment of colicin Ia. J Gen Physiol. 132(6):693-707.
Slatin SL, Finkelstein A, Kienker PK. (2008). Anomalous proton selectivity in a large channel: colicin A. Biochemistry. 47(6):1778-88.
Wu Z, Jakes KS, Samelson-Jones BS, Lai B, Zhao G, London E, Finkelstein A. (2006). Protein translocation by bacterial toxin channels: a comparison of diphtheria toxin and colicin Ia. Biophys J. 91(9):3249-56.
Krantz BA, Finkelstein A, Collier RJ. (2006). Protein translocation through the anthrax toxin transmembrane pore is driven by a proton gradient. J Mol Biol. 355(5):968-79.
Krantz BA, Melnyk RA, Zhang S, Juris SJ, Lacy DB, Wu Z, Finkelstein A, Collier RJ. (2005). A phenylalanine clamp catalyzes protein translocation through the anthrax toxin pore. Science. 309(5735):777-81.
Zhang S, Finkelstein A, Collier RJ. (2004). Evidence that translocation of anthrax toxin's lethal factor is initiated by entry of its N terminus into the protective antigen channel. Proc Natl Acad Sci U S A. 101(48):16756-61.
Zhang S, Udho E, Wu Z, Collier RJ, Finkelstein A. (2004). Protein translocation through anthrax toxin channels formed in planar lipid bilayers. Biophys J. 87(6):3842-9.
Kienker PK, Jakes KS, Blaustein RO, Miller C, Finkelstein A. (2003). Sizing the protein translocation pathway of colicin Ia channels. J Gen Physiol. 122(2):161-76.
Nassi S, Collier RJ, Finkelstein A. (2002). PA63 channel of anthrax toxin: an extended beta-barrel. Biochemistry. 41(5):1445-50.
Gordon M, Finkelstein A. (2001). The number of subunits comprising the channel formed by the T domain of diphtheria toxin. J Gen Physiol. 118(5):471-80.
Kienker PK, Jakes KS, Finkelstein A. (2000). Protein translocation across planar bilayers by the colicin Ia channel-forming domain: where will it end? J Gen Physiol. 116(4):587-98.
Senzel L, Gordon M, Blaustein RO, Oh KJ, Collier RJ, Finkelstein A. (2000). Topography of diphtheria Toxin's T domain in the open channel state. J Gen Physiol. 115(4):421-34.
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