Colicin

spinqualitylabelsall models Crystal structure of Colicin Ia, the first colicin to be identified, 1cii. Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Function Colicins are a type of bacteriocin - peptide and protein antibiotics released by bacteria to kill other bacteria of the same species, in order to provide a competitive advantage for nutrient acquisition . Bacteriocins are named after their species of origin; colicins are so-called because they are produced by E. Coli. Because of their narrow killing spectrum which focuses primarily on the species which has made the peptide (or occasionally closely related species), bacteriocins are important in microbial biodiversity and the stable co-existence of the bacterial populations. Colicin peptides are plasmid-encoded. The peptide is released by the cell into the area surrounding it, and then parasitises proteins present in the host cell membrane to translocate across into the host cell. Many protein-protein interactions are involved in the cell entry, and the main system is involved in the grouping of colicins into two families: Group A colicins use the Tol system to enter the host cell, and Group B use the Ton system. Once inside the host cell, the cell killing follows 1st order kinetics - ie one molecule is theoretically sufficient to kill the cell. Colicin-A see Colicin-A Colicin-B forms small, ion-permeable channels. It inhibits the transport of Pro and enhances the transport of methylglucoside. Colicin-D cleaves the anticodon loop of tRNAArg Colicin-E1 binds to TolC and plug channels of Gram-negative bacteria Colicin-E2 binds to BtuB and cleaves the target DNA Colicin-E3 cleaves the ribosome A site Colicin-E5 cleaves tRNA which contain the nucleotide queuosine The structure of all colicins, of which over 20 have been identified, follows a 3 domain design: At the N terminus is the Translocation domain (T-): Residues 1 to ~ 190 in ColIa. The Receptor binding domain is at the centre of the peptide (R-): Residues ~190 to 451 in ColIa. The C terminus contains the Cytotoxic domain (C-): Residues 452 to 626 in ColIa. The 3 domain structure of all colicins Some colicins exhibit DNase Activity and others TRNase activity. For more details see also Pore Formation Translocation domain H-N-H motif Colicin A 16s rRNase activity Colicin Ia Cloacin DF13. Colicin Immunity Protein Synthesis, Production and Release Synthesis of many colicins is repressed by the LexA protein, which is part of the SOS regulon. The structure of a typical colicin operon, highlighting the 3 proteins encoded together. Targeting and Receptors Colicins vary significantly in the receptors that they target to initiate their uptake. The majority of the group A colicins use the BtuB receptor, which is present on E. coli as a vitamin B12 uptake receptor. Once bound to the receptor, the coiled-coil receptor binding domain unfolds, in an essential step that removes the immunity protein and triggers translocation. Other colicins use other receptors - generally involved in the uptake of small metabolite growth factors. Colicin Uptake Colicins are divided into two groups depending on the method of uptake which they target. Group A colicins use the Tol system to bind to and enter the target cell, and group B use the Ton system. The Tol system consists of 5 proteins - TolA, TolB, TolR, TolQ and Pal, and group A proteins using this often recruit a second co-receptor involved in translocation, usually OmpF or TolC, but could be OmpC and PhoE. The Ton system consists of TonB, ExbB and ExbD, and no known co-receptor is utilised in translocation.It could be possible that Ton-dependent colicins are indiscriminate in use of coreceptors, or that the colicins move down the outside wall of a β barrel protein. It is known that colicins do unfold during translocation, but the peptides resulting from this exceed the diameter of pores formed by any of the molecules mentioned above. However, while unfolding does occur, this is not induced by receptor binding in either Tol or Ton dependent colicins. Understanding how the colicins can cross the membrane is highly important, as if this could be targeted and exploited it could be useful for novel therapeutic agents. It is also estimated that a single colicin molecule is sufficient to kill the bacterial cell, following first order kinetics. Killing Activities Colicins kill their target cell through a variety of different methods. The main killing activities are carried out through Pore Formation, DNase Activity and 16s rRNase activity, and some colicins also exhibit tRNase activity. The killing activities carried out by colicins could be used medicinally as an alternative to antibiotics in the case where the specific strain of E. coli can be identified, and as potential natural replacements for food preservatives. List of colicins, with their translocation proteins and cytotoxic activity Colicin Group OM Receptor Translocation Proteins Cytotoxic activity Immunity protein Colicin A A BtuB OmpF/TolQRAB Pore-forming Colicin_Immunity_Protein Colicin E1 A BtuB TolC/TolAQ Pore-forming ImmE1 Colicin E2 A BtuB OmpF/TolQRAB DNase Im2 Colicin E3 A BtuB OmpF/TolQRAB 16s rRNase Im3 Colicin E4 A BtuB OmpF/TolQRAB 16s rRNase Im4 Colicin E5 A BtuB OmpF/TolQRAB tRNase ImmE5 Colicin E6 A BtuB OmpF/TolQRAB 16s rRNase ImmE6 Colicin E7 A BtuB OmpF/TolQRAB DNase Im7 Colicin E8 A BtuB OmpF/TolQRAB DNase Im8 Colicin E9 A BtuB OmpF/TolQRAB DNase Im9 Colicin N A OmpF OmpF/TolQRA Pore-forming Cni Colicin S4 A OmpW OmpF/TolQRAB Pore-forming Csi Colicin K A Tsx OmpF/TolQRAB Pore-forming ? Cloacin DF13 A lutA TolQRA 16s rRNase Colicin U A ? OmpAF, TolQRAB Pore-forming Cui Colicin 5 B Tsx TolC/TonB, ExbBD Pore-forming Cfi Colicin 6 B Tsx TolC/TonB, ExbBD Pore-forming ? Colicin 7 B Tsx TolC/TonB, ExbBD Pore-forming ? Colicin 8 B Tsx TolC/TonB, ExbBD Pore-forming ? Colicin 9 B Tsx TolC/TonB, ExbBD Pore-forming ? Colicin 10 B Tsx TolC/TonB, ExbBD Pore-forming Cti Colicin Ia B Cir Cir/TonB, ExbBD Pore-forming Iia Colicin Ib B Cir Cir/TonB, ExbBD Pore-forming Imm Colicin B B FepA ?/TonB, ExbBD Pore-forming Cbi Colicin D B FepA ?/TonB, ExbBD tRNase ImmD Colicin M B FhuA ?/TonB, ExbBD Inhibition of PG synthesis Cmi Colicin V B Cir? TonB, ExbB Disruption of membrane potential Cvi Colicin Js B CjrBC ExbBD, VirB ? Cji Colicin Y ? ? ? Pore-forming Cyi Table taken from except where indicated. 3D structure of Colicin Colicin 3D structures

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