Mechanism of pore formation by ClyA
Pore forming toxins are proteins that exist in a water soluble, usually monomeric form, and oligomerize in the presence of lipids or biological membranes to form transmembrane pores . These pores allow the passage of material from the eukaryotic cell, leading to cell lysis. Working with collaborators in the Depts of Chemical Engineering, Physics, and the Centre for Biosystems Science and Engineering, we have been studying the mechanism by which Cytolysin A (ClyA) forms pores. We have identified regions of the protein important for oligomerization, and using single molecule TIRF microscopy on supported lipid bilayers and molecular dynamic simulations, we have studied the dynamics of oligomerization and the role of cholesterol in stabilizing intermediates during pore formation.
Sathyanarayana, P., Maurya, S., Behera, A., Ravichandran, M., Visweswariah, S.S., Ayappa, K.G. and Roy, R (2018) Cholesterol promotes Cytolysin A activity by stabilizing the intermediates during pore formation. Proc. Natl. Acad. Sci. (USA) www.pnas.org/cgi/doi/10.1073/pnas.1721228115
Sarangi NK, Ayappa KG, Visweswariah SS, Basu JK (2016) Super-resolution Stimulated Emission Depletion-Fluorescence Correlation Spectroscopy Reveals Nanoscale Membrane Reorganization Induced by Pore-Forming Proteins Langmuir 32 : 9649-9657
Sarangi NK, Ayappa KG, Visweswariah SS, Basu JK (2016) Nanoscale dynamics of phospholipids reveals an optimal assembly mechanism of pore-forming proteins in bilayer membranes Physical Chemistry Chemical Physics 18 (43), 29935-29945
Sathyanarayana P, Desikan,R, Ayappa, KG and Visweswariah, SS (2016) The Solvent-Exposed C-Terminus of the Cytolysin A Pore-Forming Toxin Directs Pore Formation and Channel Function in Membranes Biochemistry 55: 5952-5961
Vaidyanathan, M.S., Sathyanarayana, P. Maiti, P.K., Visweswariah, S.S. and Ayappa, K.G. (2014) Lysis dynamics and membrane oligomerizationpathways for Cytolysin A (ClyA) pore-forming toxin. RSC Adv, 4: 4930-4942.