Dr. Audette, Gerald
Presentation day
Wednesday 4:40 PM
TITLE
Dimerization of the type IV pilin from Pseudomonas aeruginosa strain K122-4 and it's
oligomerization into protein nanotubes
Abstract
Self-assembling protein nanotubes (PNTs) are an intriguing alternative to carbon
nanotubes for applications in bionanotechnology, in part due to greater inherent biocompatibility. The type
IV pilus of the gram negative bacteria Pseudomonas aeruginosa is a protein-based fibre composed of a
single monomeric subunit, the type IV pilin. Engineered pilin monomers from P. aeruginosa strain K122-4
(ΔK122) have been shown to oligomerize into PNTs both in solution and at surfaces. In order to fully exploit
PNTs in bionanotechonological settings, an in-depth understanding of their assembly, physical
characteristics, robustness etc., both in solution and when constrained to surfaces, is required.
Characterization of the oligomerization process in solution has revealed that protein is in a monomer-dimer
equilibrium in solution, that the optimal initiator is 2-methyl-2,4-pentanediol (MPD), and that PNT
oligomerization is a fibril-mediated process. Examination of the structural changes occurring between the
monomeric and dimeric states of ΔK122 using time-resolved hydrogen-deuterium exchange mass
spectrometry reveals that, based on levels of deuterium uptake, the N-terminal α-helix and the loop
connecting the second and third strands of the anti-parallel β-sheet contribute significantly to pilin
dimerization. Conversely, the antiparallel β-sheet and αβ loop region exhibit increased flexibility, while the
receptor binding domain retains a rigid conformation in the equilibrium state.
Literatures
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Clinical Nanomedicine: Nanoparticles, Imaging, Therapy and Clinical Applications; Pan Sanford Series on Nanomedicine, Vol. 1; Raj Bawa, Gerald F. Audette & Israel Rubinstein (eds.); Pan Sanford Publishing, Singapore (2016)
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Handbook of Clinical Nanomedicine: Law, Business, Regulation, Safety and Risk; Pan Sanford Series on Nanomedicine, Vol. 2; Raj Bawa, Gerald F. Audette & Brian E. Reese (eds.); Pan Sanford Publishing, Singapore (2016)
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Lento, C., Wilson, D. & Audette, G.F. Dimerization of the type IV pilin from Pseudomonas aeruginosa strain K122-4 results in increased helix stability as measured by Time-Resolved Hydrogen-Deuterium Exchange. Structural Dynamics 3(1): 012001 (2016)
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Dudzik, J., Chang, W.-C., Kannan, A.M., Filipek, A., Viswanathan, S., Li, P., Renugopalakrishnan & Audette, G.F. Cross-Linked Glucose Oxidase Clusters for Biofuel Cell Anode Catalysts. Biofabrication 5: 035009 (2013)
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Petrov, A., Lombardo, S. & Audette, G.F. Fibril-Mediated Oligomerization of Pilin-derived Protein Nanotubes. J. Nanobiotechnol. 11:24 (2013)
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Petrov. A. & Audette, G.F. Peptide & Protein Nanotubes for Bionanotechnology. WIREs Nanomed Nanobiotechnol 4, 575-585 (2012)
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Lombardo, S., Zahedijasbi, S., Jeung, S.-K., Morin, S. & Audette, G.F. Initial Studies of Protein Nanotube Oligomerization from a Modified Gold Surface. J. Bionanosci. 3(1), 61-65 (2009).
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Kannan, A.M., Renugopalakrishnan, V., Filipek, S., Li, P., Audette, G.F. & Munukutla, L. Bio-Batteries and Bio-Fuel Cells: Leveraging on Electronic Charge Transfer Proteins. J. Nanosci. Nanotechnol. 9(3), 1665-1678 (2009)
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Yu, B., Giltner, C.L., van Schaik, E.J., Bautista, D.L., Hodges, R.S., Audette, G.F., Li, D.Y., & Irvin, R.T. A Novel Biometallic Interface: High Affinity Tip-Associated Binding by Pilin-Derived Protein Nanotubes. J. Bionanosci. 1(2), 73-83 (2009)
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Audette, G.F. & Hazes, B. Development of Protein Nanotubes from a Multi-Purpose Biological Structure. J. Nanosci. Nanotechnol. 7(7), 2222-2229 (2007)
CV
2001: PhD (Biochemistry), University of Saskatchewan (Canada)
2001 – 2004: Post-doctoral Fellowship, Dept. of Medical Microbiology, University of Alberta (Canada)
2004 – 2006: Post-doctoral Fellowship, Depts. of Biological Sciences & Medical Microbiology, University of Alberta (Canada)
2006: Assistant Professor, Dept. of Chemistry, York University (Canada)
2007: Centre for Research on Biomolecular Interactions, York University
2007-2010: Co-Editor-in-Chief, Journal of Bionanoscience
2011: Associate Professor, Department of Chemistry, York University
2014: Undergraduate Program Director, Dept. of Chemistry, York University
2014: Graduate Mentorship Award, Faculty of Science, York University
2014-2015: Acting Director of the Centre for Research on Biomolecular Interactions, York University