Colicin

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PDB ID 2k5x

Drag the structure with the mouse to rotate
2k5x, 1 NMR models ()
Gene: imm, ceiE9 (Escherichia coli), col, cei (Escherichia coli)
Related: 1imq, 1fsj, 1emv
Resources: FirstGlance, OCA, PDBsum, RCSB
Coordinates: save as pdb, mmCIF, xml


Colicins are a type of bacteriocin - peptide and protein antibiotics released by bacteria to kill other bacteria of the same species. Bacteriocins are named after their species of origin; colicins are so-called because they are produced by E. Coli[1]. Because of their narrow killing spectrum which focuses primarily on the species which has made the peptide, 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.

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-)
The Receptor binding domain is at the centre of the peptide (R-)
The C terminus contains the Cytotoxic domain (C-).

Image:Colicin_Domain_structure.png

Contents

Synthesis and Production

Release

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.

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. [2]

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.

Killing Activities

Colicins kill their target cell through a variety of different methods. The main killing activities are carried out through Pore Formation, and 16s rRNase 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. [3]


List of colicins, with their translocation proteins and cytotoxic activity
Colicin Group OM Receptor Translocation Proteins Cytotoxic activity
Colicin A A BtuB OmpF/TolQRAB Pore-forming
Colicin E1 A BtuB TolC/TolAQ Pore-forming
Colicin E2 A BtuB OmpF/TolQRAB DNase
Colicin E3 A BtuB OmpF/TolQRAB 16s rRNase
Colicin E4 A BtuB OmpF/TolQRAB 16s rRNase
Colicin E5 A BtuB OmpF/TolQRAB tRNase
Colicin E6 A BtuB OmpF/TolQRAB 16s rRNase
Colicin E7 A BtuB OmpF/TolQRAB DNase
Colicin E8 A BtuB OmpF/TolQRAB DNase
Colicin E9 A BtuB OmpF/TolQRAB DNase
Colicin N A OmpF OmpF/TolQRA Pore-forming
Colicin S4 A OmpW OmpF/TolQRAB Pore-forming
Colicin K A Tsx OmpF/TolQRAB Pore-forming
Cloacin DF13 A lutA [4] TolQRA [5] 16s rRNase [6]
Colicin U A  ? OmpAF, TolQRAB Pore-forming
Colicin 5 B Tsx TolC/TonB, ExbBD Pore-forming
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
Colicin Ia B Cir Cir/TonB, ExbBD Pore-forming
Colicin Ib B Cir Cir/TonB, ExbBD Pore-forming
Colicin B B FepA  ?/TonB, ExbBD Pore-forming
Colicin D B FepA  ?/TonB, ExbBD tRNase
Colicin M B FhuA  ?/TonB, ExbBD Inhibition of PG synthesis
Colicin V B Cir? [7] TonB, ExbB Disruption of membrane potential
Colicin Js B CjrBC [8] ExbBD, VirB [9]  ?
Colicin Y  ?  ?  ? Pore-forming [10]

Table taken from [11] except where indicated.

References

  1. Cascales E, Buchanan SK, Duche D, Kleanthous C, Lloubes R, Postle K, Riley M, Slatin S, Cavard D. Colicin biology. Microbiol Mol Biol Rev. 2007 Mar;71(1):158-229. PMID:17347522 doi:10.1128/MMBR.00036-06
  2. Mosbahi K, Walker D, Lea E, Moore GR, James R, Kleanthous C. Destabilization of the colicin E9 Endonuclease domain by interaction with negatively charged phospholipids: implications for colicin translocation into bacteria. J Biol Chem. 2004 May 21;279(21):22145-51. Epub 2004 Mar 23. PMID:15044477 doi:10.1074/jbc.M400402200
  3. Cutler SA, Lonergan SM, Cornick N, Johnson AK, Stahl CH. Dietary inclusion of colicin e1 is effective in preventing postweaning diarrhea caused by F18-positive Escherichia coli in pigs. Antimicrob Agents Chemother. 2007 Nov;51(11):3830-5. Epub 2007 Aug 27. PMID:17724148 doi:10.1128/AAC.00360-07
  4. Wooldridge KG, Williams PH. Sensitivity of Escherichia coli to cloacin DF13 involves the major outer membrane protein OmpF. J Bacteriol. 1991 Apr;173(8):2420-4. PMID:2013565
  5. Thomas JA, Valvano MA. Role of tol genes in cloacin DF13 susceptibility of Escherichia coli K-12 strains expressing the cloacin DF13-aerobactin receptor IutA. J Bacteriol. 1993 Jan;175(2):548-52. PMID:8419302
  6. Baan RA, Duijfjes JJ, van Leerdam E, van Knippenberg PH, Bosch L. Specific in situ cleavage of 16S ribosomal RNA of Escherichia coli interferes with the function of initiation factor IF-1. Proc Natl Acad Sci U S A. 1976 Mar;73(3):702-6. PMID:768982
  7. Waters VL, Crosa JH. Colicin V virulence plasmids. Microbiol Rev. 1991 Sep;55(3):437-50. PMID:1943995
  8. Braun V, Patzer SI, Hantke K. Ton-dependent colicins and microcins: modular design and evolution. Biochimie. 2002 May-Jun;84(5-6):365-80. PMID:12423780
  9. Smajs D, Weinstock GM. The iron- and temperature-regulated cjrBC genes of Shigella and enteroinvasive Escherichia coli strains code for colicin Js uptake. J Bacteriol. 2001 Jul;183(13):3958-66. PMID:11395459 doi:10.1128/JB.183.13.3958-3966.2001
  10. Riley MA, Cadavid L, Collett MS, Neely MN, Adams MD, Phillips CM, Neel JV, Friedman D. The newly characterized colicin Y provides evidence of positive selection in pore-former colicin diversification. Microbiology. 2000 Jul;146 ( Pt 7):1671-7. PMID:10878131
  11. Kleanthous C. Swimming against the tide: progress and challenges in our understanding of colicin translocation. Nat Rev Microbiol. 2010 Dec;8(12):843-8. Epub 2010 Nov 9. PMID:21060316 doi:10.1038/nrmicro2454

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