Poster Presentation The 3rd Prato Conference on Pore Forming Proteins 2015

Properties of Colicin U pores investigated using cysteine mutations (#37)

Tereza Dolejšová 1 , Juraj Bosák 2 , David Šmajs 2 , Ivo Konopásek 1 , Radovan Fišer 1
  1. Faculty of Science Charles University in Prague, Prague, Czech Republic
  2. Faculty of Medicine, Masaryk University, Brno, Czech Republic

Colicin U is a putative pore-forming toxin produced by bacterium Shigella boydii (serovars 1 and 8). It exhibits antibacterial activity against the strains of Gram-negative enterobacteria of genus Shigella and Escherichia. The proposed mechanism of Colicin U interaction with the target cells includes three steps i) binding to the surface receptors OmpA, OmpF and core lipopolysacharide ii) translocation through outer membrane via Tol proteins and iii) final antibacterial action. A high degree of homology between the C-terminal part of Colicin U and pore-forming colicins A and B was described. Using single channel recording on the planar lipid membranes (BLM) we have already confirmed that Colicin U is able to create very stable pores with well-defined conductance (20pS in 1M KCl, pH 6), when negative potential (>40mV) was applied. The conductance of pores is significantly affected by anions since the Colicin U pores exhibit only moderate cation selectivity (Rb> Na> K> Li+). We also focused on the effect of nonelectrolytes on the ion permeability of pores in order to estimate the pore diameter. Glycerol passed through the pores and decreased the conductance while PEG300 molecules were unable to enter the pore interior. Therefore, the estimated pore diameter was about 0.7 nm. Additionally, we created several mutants of Colicin U with point substitutions to cysteine at different positions of pore-forming domain (F463C, D486C, F504C, V532C, W545C). Stability of pores with mutation V532C or W545C is distinct from the wild type pore. Therefore we suppose that these two amino acids could be involved in formation of the pore. Subsequently we plan to use the cysteine mutations for further topology screening.