The Krantz laboratory is interested broadly in the basic science and biophysical chemistry of membrane proteins involved in cellular transport and trafficking. These basic science research interests and the particular model systems studied are also meant to translate into wider Biosecurity and Biodefense applications.

• Transmembrane protein translocation. Elucidating the mechanism of protein translocation by bacterial toxins, such as anthrax toxin, will: broaden our basic understanding of protein transport across membranes, further countermeasure development, and allow the toxin to be adapted as a means for targeted protein and small-molecule drug delivery. The laboratory is currently using single-channel electrophysiology and structural studies to understand how a series of polypeptide clamp structures work cooperatively to promote efficient unfolding and translocation.

• In vivo architecture of anthrax toxin. Understanding the macromolecular architecture of anthrax toxin complexes during an infection is critical not only to the development of vaccines and the passive immunotherapeutics but also to understanding anthrax pathogenesis. The laboratory is currently using electron microscopy and mass spectrometry to develop means of studying anthrax toxin isolated from in vivo animal models.

• Nanopore toxicant sensing. Working toward deeper insight on the structure and function of the anthrax toxin nanopore, and other similar systems, will ultimately enable the creation of a multiplexed sensor array, or bioelectronic nose, capable of detecting toxic analytes in clinical samples, key industrial processes, the food supply, and the environment.

• Pore-forming toxins of periodontal disease. The etiology of periodontal disease is highly complex since over 500 species of bacteria populate the oral cavity. However, a smaller subset of pathogenic bacteria can populate a diseased periodontal pocket, releasing a storm of toxic substances, including pore-forming toxins, which lead not only to localized inflammation, tissue damage, and tooth loss but also to systemic inflammation (leading to atherosclerosis) and neuroinflammation (leading to dementia). Understanding these toxins will enable insights on pathogenesis.

Selected Publications

Wynia Smith SL, Brown MJ, Chirichella G, Krantz BA. (2012) "Electrostatic Ratchet In The Protective Antigen Channel Promotes Anthrax Toxin Translocation." J. Biol. Chem. 287: 43753.

Kintzer AF, Tang II, Schawel AK, Brown MJ, Krantz BA. (2012) "Anthrax toxin protective antigen integrates poly-γ-d-glutamate and pH signals to sense the optimal environment for channel formation." Proc. Natl Acad. Sci. 109: 18378.

Feld GK, Brown MJ, Krantz BA. (2012) "Ratcheting up protein translocation with anthrax toxin." Protein Sci.   21: 606.

Brown MJ, Thoren KL, Krantz BA. (2011) "Charge requirements for proton gradient-driven translocation of anthrax toxin." J Biol Chem. 286: 23189.

Feld GK, Thoren KL, Kintzer AF, Sterling HJ, Tang II, Greenberg SG, Williams ER, Krantz BA. (2010) "Structural basis for the unfolding of anthrax lethal factor by protective antigen oligomers." Nature Struct. Mol. Biol. 17: 1383.

Thoren KL, Worden EJ, Yassif JM, Krantz BA. (2009) "Lethal factor unfolding is the most force-dependent step of anthrax toxin translocation." Proc. Natl Acad. Sci. 106: 21555.

Kintzer AF, Thoren KL, Sterling HJ, Dong KC, Feld GK, Tang II, Zhang TT, Williams ER, Berger JM, Krantz BA. (2009) "The protective antigen component of anthrax toxin forms functional octameric complexes." J. Mol. Biol. 392: 614.

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: 968.

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: 777.