A colicin is a type of

bacteriocin Bacteriocins are proteinaceous or peptide, 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 ...

produced by and toxic to some strains of ''

Escherichia coli ''Escherichia coli'' ( )Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. is a gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Escherichia'' that is commonly fo ...

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

bacterial strain Bacteria (; : bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among the fi ...

s. Colicins bind to outer membrane receptors, 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 the ...

activity, or inhibition of murein synthesis.

Structure

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

transmembrane protein A transmembrane protein 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 frequently un ...

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 (T domain); a central domain responsible for receptor recognition (R domain); and a C-terminal

cytotoxic Cytotoxicity is the quality of being toxic to cells. Examples of toxic agents are toxic metals, toxic chemicals, microbe neurotoxins, radiation particles and even specific neurotransmitters when the system is out of balance. Also some types of dr ...

domain responsible for channel formation in the cytoplasmic membrane (C domain). R domain regulates the target and binds to the receptor on the sensitive cell. T domain is involved in translocation, co-opting the machinery of the target cell. The C domain is the 'killing' domain and may produce a pore in the target

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

, or act as a

nuclease In biochemistry, a nuclease (also archaically known as nucleodepolymerase or polynucleotidase) is an enzyme capable of cleaving the phosphodiester bonds that link nucleotides together to form nucleic acids. Nucleases variously affect single and ...

to chop up the

DNA Deoxyribonucleic acid (; DNA) is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of al ...

RNA Ribonucleic acid (RNA) is a polymeric molecule that is essential for most biological functions, either by performing the function itself (non-coding RNA) or by forming a template for the production of proteins (messenger RNA). RNA and deoxyrib ...

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 receptor (biochemistry), receptors that are embedded in the cell membrane, plasma membrane of cell (biology), cells. They act in cell signaling by receiving (binding to) ex ...

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; it has symbol Fe () 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, forming much of Earth's o ...

or a

B vitamin B vitamins are a class of water-soluble vitamins that play important roles in cell metabolism and synthesis of red blood cells. They are a chemically diverse class of compounds. Dietary supplements containing all eight are referred to as a vit ...

), 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 is the cumulative effect produced when one event sets off a series of similar or related events, a form of chain reaction. The term is an analogy to a falling row of dominoes. It typically refers to a linked sequence of events ...

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 poison produced by metabolic activities of living cells or organisms. They occur especially as proteins, often conjugated. The term was first used by organic chemist Ludwig Brieger (1849–1919), derived ...

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 and ...

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 has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

s. These include a colicin structural gene, an immunity gene, and a bacteriocin release protein (BRP), or

lysis Lysis ( ; from Greek 'loosening') 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 ...

, 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, 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 messenger RNA correspond to the additio ...

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

SOS response The SOS response is a global transcriptional response to DNA damage in prokaryotes, in which the cell cycle is arrested and DNA repair mechanisms (error-free as well as error-prone) are induced. The regulation of this response is driven by two p ...

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

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

University of Oxford The University of Oxford is a collegiate university, collegiate research university in Oxford, England. There is evidence of teaching as early as 1096, making it the oldest university in the English-speaking world and the List of oldest un ...

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