Research Interests

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 model systems studied are also meant to translate into wider nanopore biosensing and sequencing applications.

  • Transmembrane protein translocation. Elucidating the mechanism of protein translocation using model systems, 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.
  • Nanopore biosensing. 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 and peptides in clinical samples, key industrial processes, the food supply, and the environment. Advanced computational methods (Deep Learning and Machine Learning) are being used to process large datasets and classify samples.
  • Nanopore peptide sequencing. We are investigating the feasibility of Deep Learning-enabled nanopore protein sequencing. Using protein engineering and advanced deep learning methods, we will identify and interpret amino acid-specific signatures within real multi-state polypeptide translocation events, establishing the experimental and computational foundation for nanopore protein sequencing.
  • Co-complexes of poly-glutamic acid capsule and anthrax toxin subunits. Pathogenic strains of Bacillus anthracissecrete a poly-glutamic acid virulence factor in animal models that consists of long, linear polypeptides of ᴅ-Glu polymerized via amide linkages between the γ-carboxylate and α-amino group of adjacent monomers. These polymers, which can be cleaved into smaller polypeptides, can bind to all three anthrax toxin subunits. We want to better understand how theses co-complexes guide anthrax toxin assembly and re-direct the toxin during trafficking into the host cell.
Selected Publications

Krantz BA. (2024) "Anthrax Toxin: Model System for Studying Protein Translocation." J Mol Biol. 436: 168521.

Hardenbrook NJ, Liu S, Zhou K, Ghosal K, Zhou ZH, Krantz BA. (2020) "Atomic structures of anthrax toxin protective antigen channels bound to partially unfolded lethal and edema factors." Nat. Commun. 11: 840.

Ghosal K, Colby JM, Das D, Joy ST, Arora PS, Krantz BA. (2017) "Dynamic Phenylalanine Clamp Interactions Define Single-Channel Polypeptide Translocation through the Anthrax Toxin Protective Antigen Channel." J. Mol. Biol. 429: 900.

Das D, Krantz BA. (2017) "Secondary Structure Preferences of the Anthrax Toxin Protective Antigen Translocase." J. Mol. Biol. 429: 753.

Das D, Krantz BA. (2016) "Peptide- and proton-driven allosteric clamps catalyze anthrax toxin translocation across membranes." Proc. Natl Acad. Sci. 113: 9611.

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.