A colicin is a type of

bacteriocin Bacteriocins are proteinaceous or peptidic toxins produced by bacteria to inhibit the growth of similar or closely related bacterial strain(s). They are similar to yeast and paramecium killing factors, and are structurally, functionally, and ec ...

produced by and toxic to some strains of ''

Escherichia coli ''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus ''Escher ...

''. Colicins are released into the environment to reduce competition from other bacterial strains. Colicins bind to

outer membrane receptor Outer membrane receptors, also known as TonB-dependent receptors, are a family of beta barrel proteins named for their localization in the outer membrane of gram-negative bacteria. TonB complexes sense signals from the outside of bacterial cells ...

s, using them to translocate to the cytoplasm or cytoplasmic membrane, where they exert their cytotoxic effect, including depolarisation of the cytoplasmic membrane,

DNase Deoxyribonuclease (DNase, for short) refers to a group of glycoprotein endonucleases which are enzymes that catalyze the hydrolytic cleavage of phosphodiester linkages in the DNA backbone, thus degrading DNA. The role of the DNase enzyme in cells ...

activity,

RNase Ribonuclease (commonly abbreviated RNase) is a type of nuclease that catalyzes the degradation of RNA into smaller components. Ribonucleases can be divided into endoribonucleases and exoribonucleases, and comprise several sub-classes within t ...

activity, or inhibition of

murein Peptidoglycan or murein is a unique large macromolecule, a polysaccharide, consisting of sugars and amino acids that forms a mesh-like peptidoglycan layer outside the plasma membrane, the rigid cell wall (murein sacculus) characteristic of most ba ...

synthesis.

Structure

Channel-forming colicins (colicins A, B, E1, Ia, Ib, and N) are

transmembrane protein A transmembrane protein (TP) is a type of integral membrane protein that spans the entirety of the cell membrane. Many transmembrane proteins function as gateways to permit the transport of specific substances across the membrane. They frequentl ...

s that depolarize the cytoplasmic membrane, leading to dissipation of cellular energy. These colicins contain at least three domains: an N-terminal translocation domain responsible for movement across the outer membrane and

periplasmic space The periplasm is a concentrated gel-like matrix in the space between the inner cytoplasmic membrane and the bacterial outer membrane called the ''periplasmic space'' in gram-negative bacteria. Using cryo-electron microscopy it has been found tha ...

; a central domain responsible for receptor recognition; and a C-terminal

cytotoxic Cytotoxicity is the quality of being toxic to cells. Examples of toxic agents are an immune cell or some types of venom, e.g. from the puff adder (''Bitis arietans'') or brown recluse spider (''Loxosceles reclusa''). Cell physiology Treating cells ...

domain responsible for channel formation in the cytoplasmic membrane. One domain regulates the target and binds to the receptor on the sensitive cell. The second is involved with translocation, co-opting the machinery of the target cell. The third is the 'killing' domain and may produce a pore in the target

cell membrane The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment ( ...

, or act as a nuclease to chop up the DNA or

RNA Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid ( DNA) are nucleic acids. Along with lipids, proteins, and carbohydra ...

of the target cell.

Translocation

Most colicins are able to translocate the outer membrane by a two-receptor system, where one receptor is used for the initial binding and the second for translocation. The initial binding is to

cell surface receptors Cell surface receptors (membrane receptors, transmembrane receptors) are receptors that are embedded in the plasma membrane of cells. They act in cell signaling by receiving (binding to) extracellular molecules. They are specialized integral m ...

such as the outer membrane proteins OmpF, FepA, BtuB, Cir and FhuA; colicins have been classified according to which receptors they bind to. The presence of specific periplasmic proteins, such as TolA, TolB, TolC, or TonB, are required for translocation across the membrane. Cloacin DF13 is a bacteriocin that inactivates ribosomes by hydrolysing 16S RNA in 30S ribosomes at a specific site.

Resistance

Because they target specific receptors and use specific translocation machinery, cells can make themselves resistant to the colicin by repressing or deleting the genes for these proteins. Such resistant cells may suffer the lack of a key nutrient (such as

iron Iron () is a chemical element with symbol Fe (from la, ferrum) and atomic number 26. It is a metal that belongs to the first transition series and group 8 of the periodic table. It is, by mass, the most common element on Earth, right in f ...

or a

B vitamin B vitamins are a class of water-soluble vitamins that play important roles in Cell (biology), cell metabolism and synthesis of red blood cells. Though these vitamins share similar names (B1, B2, B3, etc.), they are chemically distinct compounds th ...

), but benefit by not being killed. Colicins exhibit a '1-hit killing kinetic' which does not necessarily mean a single molecule is sufficient to kill, but certainly that it only takes a small number. In his 1969 Nobel Laureate speech, Salvador E. Luria speculated that colicins could only be this toxic by causing a

domino effect A domino effect or chain reaction is the cumulative effect generated when a particular event triggers a chain of similar events. This term is best known as a mechanical effect and is used as an analogy to a falling row of dominoes. It typically ...

that destabilized the cell membrane. He was not entirely correct, but pore-forming colicins do depolarize the membrane and thus eliminate the energy source for the cell. The colicins are highly effective

toxin A toxin is a naturally occurring organic poison produced by metabolic activities of living cells or organisms. Toxins occur especially as a protein or conjugated protein. The term toxin was first used by organic chemist Ludwig Brieger (1849– ...

Genetic organisation

Virtually all colicins are carried on

plasmid A plasmid is a small, extrachromosomal DNA molecule within a cell that is physically separated from chromosomal DNA and can replicate independently. They are most commonly found as small circular, double-stranded DNA molecules in bacteria; how ...

s. The two general classes of colicinogenic plasmids are large, low-copy-number plasmids, and small, high-copy-number plasmids. The larger plasmids carry other genes, as well as the colicin operon. The colicin operons are generally organized with several major

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

s. These include an immunity gene, a colicin structural gene, and a

bacteriocin release protein Bacteriocins are proteinaceous or peptidic toxins produced by bacteria to inhibit the growth of similar or closely related bacterial strain(s). They are similar to yeast and paramecium killing factors, and are structurally, functionally, and ec ...

(BRP), or

lysis Lysis ( ) is the breaking down of the membrane of a cell, often by viral, enzymic, or osmotic (that is, "lytic" ) mechanisms that compromise its integrity. A fluid containing the contents of lysed cells is called a ''lysate''. In molecular bio ...

, gene. The immunity gene is often produced constitutively, while the BRP is generally produced only as a read-through of the

stop codon In molecular biology (specifically protein biosynthesis), a stop codon (or termination codon) is a codon (nucleotide triplet within messenger RNA) that signals the termination of the translation process of the current protein. Most codons in me ...

on the colicin structural gene. The colicin itself is repressed by the

SOS response The SOS response is a global response to DNA damage in which the cell cycle is arrested and DNA repair and mutagenesis is induced. The system involves the RecA protein ( Rad51 in eukaryotes). The RecA protein, stimulated by single-stranded DNA, ...

and may be regulated in other ways, as well. Retaining the colicin plasmid is very important for cells that live with their relatives, because if a cell loses the immunity gene, it quickly becomes subject to destruction by circulating colicin. At the same time, colicin is only released from a producing cell by the use of the lysis protein, which results in that cell's death. This suicidal production mechanism would appear to be very costly, except for the fact that it is regulated by the

, which responds to significant DNA damage. In short, colicin production may only occur in terminally ill cells. The Professor Kleanthous Research Group at the

University of Oxford , mottoeng = The Lord is my light , established = , endowment = £6.1 billion (including colleges) (2019) , budget = £2.145 billion (2019–20) , chancellor ...

study colicins extensively as a model system for characterising and investigating protein-protein interactions and recognition. BACTIBASE database is an open-access database for bacteriocins including colicins
view complete list
.

References

External links

Molecular mechanisms of colicin evolutionpdf

The newly characterized colicin Y provides evidence of positive selection in pore-former colicin diversification

Colicin OPM database

3D interactive pages about colicins

Transport Classification Database listing for colicin

Protein Data Bank colicin listing
{{InterPro content, IPR000290 Bacteriocins Toxicology Peripheral membrane proteins Escherichia coli