A ribosome-inactivating protein (RIP) is a

protein synthesis inhibitor A protein synthesis inhibitor is a compound that stops or slows the growth or proliferation of cells by disrupting the processes that lead directly to the generation of new proteins. While a broad interpretation of this definition could be used t ...

that acts at the

eukaryotic Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacte ...

ribosome Ribosomes ( ) are macromolecular machines, found within all cells, that perform biological protein synthesis (mRNA translation). Ribosomes link amino acids together in the order specified by the codons of messenger RNA (mRNA) molecules to ...

. This

protein family A protein family is a group of evolutionarily related proteins. In many cases, a protein family has a corresponding gene family, in which each gene encodes a corresponding protein with a 1:1 relationship. The term "protein family" should not be c ...

describes a large family of such proteins that work by acting as rRNA N-glycosylase (EC 3.2.2.22). They inactivate 60S ribosomal subunits by an N-glycosidic cleavage, which releases a specific

adenine Adenine () ( symbol A or Ade) is a nucleobase (a purine derivative). It is one of the four nucleobases in the nucleic acid of DNA that are represented by the letters G–C–A–T. The three others are guanine, cytosine and thymine. Its derivati ...

base from the sugar-phosphate backbone of 28S

rRNA Ribosomal ribonucleic acid (rRNA) is a type of non-coding RNA which is the primary component of ribosomes, essential to all cells. rRNA is a ribozyme which carries out protein synthesis in ribosomes. Ribosomal RNA is transcribed from ribosoma ...

. RIPs exist in bacteria and plants. Members of the family include

shiga toxin Shiga toxins are a family of related toxins with two major groups, Stx1 and Stx2, expressed by genes considered to be part of the genome of lambdoid prophages. The toxins are named after Kiyoshi Shiga, who first described the bacterial orig ...

s, and type I (e.g.

trichosanthin Trichosanthin is a ribosome-inactivating protein. It is derived from ''Trichosanthes kirilowii''. It is also an abortifacient An abortifacient ("that which will cause a miscarriage" from Latin: ''abortus'' "miscarriage" and '' faciens'' "maki ...

and luffin) and type II (e.g.

ricin Ricin ( ) is a lectin (a carbohydrate-binding protein) and a highly potent toxin produced in the seeds of the castor oil plant, ''Ricinus communis''. The median lethal dose (LD50) of ricin for mice is around 22 micrograms per kilogram of body ...

agglutinin An agglutinin is a substance in the blood that causes particles to coagulate and aggregate; that is, to change from fluid-like state to a thickened-mass (solid) state. Agglutinins can be antibodies that cause antigens to aggregate by binding t ...

, and

abrin Abrin is an extremely toxic toxalbumin found in the seeds of the rosary pea (or jequirity pea), ''Abrus precatorius''. It has a median lethal dose of 0.7 micrograms per kilogram of body mass when given to mice intravenously (approximately ...

) ribosome inactivating proteins (RIPs). All these toxins are structurally related. RIPs have been of considerable interest because of their potential use, conjugated with monoclonal antibodies, as

immunotoxin An immunotoxin is an artificial protein consisting of a targeting portion linked to a toxin. When the protein binds to that cell, it is taken in through endocytosis, and the toxin kills the cell. They are used for the treatment of some kinds of c ...

s to treat

cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...

s. Further,

has been shown to have potent activity against

HIV-1 The subtypes of HIV include two major types, HIV type 1 (HIV-1) and HIV type 2 (HIV-2). HIV-1 is related to viruses found in chimpanzees and gorillas living in western Africa, while HIV-2 viruses are related to viruses found in the sooty mangabey, ...

-infected

T cells A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell re ...

and

macrophage Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer cel ...

s. Elucidation of the structure-function relationships of RIPs has therefore become a major research effort. It is now known that RIPs are structurally related. A conserved glutamic residue has been implicated in the catalytic mechanism; this lies near a conserved arginine, which also plays a role in catalysis. Only a minority of RIPs are toxic to humans when consumed, and proteins of this family are found in the vast majority of plants used for human consumption, such as Rice, Maize and Barley. In plants, they are thought to defend against pathogens and insects. Ribosome-inactivating proteins (RIPs) are separated into the following types based on protein domain composition: * Type I (A): RIPs-I are polypeptides composed of an A domain. This is the site of N-glycosidase activity. * Type II (AB): RIPs-II are composed of an A domain with similar catalytic activity to Type I RIPs, and a B domain with carbohydrate-binding (lectin) properties. The B domain is able to bind galactosyl moieties on the cell surface which facilitates entry into the cell, thus making Type II particularly cytotoxic. The A and B domains are fused together by disulfide bonds. This group excludes bacterial

AB5 toxin The AB5 toxins are six-component protein complexes secreted by certain pathogenic bacteria known to cause human diseases such as cholera, dysentery, and hemolytic–uremic syndrome. One component is known as the A subunit, and the remaining fiv ...

s such as Shiga toxin, as the carbohydrate-binding ability evolved separately and these toxins are more similar to type I RIPs. * Type III: RIPs-III are separated into two subgroups. One subgroup (AC) contains the same original RIP domain (A), and a C-terminal with unknown functionality. The other subgroup (AD) is similar to Type I, but contains a site for inactivation. Examples include: *

Abrin Abrin is an extremely toxic toxalbumin found in the seeds of the rosary pea (or jequirity pea), ''Abrus precatorius''. It has a median lethal dose of 0.7 micrograms per kilogram of body mass when given to mice intravenously (approximately ...

Beetin Beetin (BE27 or BE29) is a ribosome-inactivating protein found in the leaves of sugar beets, ''Beta vulgaris'' L, specifically attacking plant ribosomes. Sugar beet, beetins, that have been isolated meet all the criteria to be classified as sing ...

Ricin Ricin ( ) is a lectin (a carbohydrate-binding protein) and a highly potent toxin produced in the seeds of the castor oil plant, ''Ricinus communis''. The median lethal dose (LD50) of ricin for mice is around 22 micrograms per kilogram of body ...

Saporin Saporin is a protein that is useful in biological research applications, especially studies of behavior. Saporins are so-called ribosome inactivating proteins (RIPs), due to its N-glycosidase activity, from the seeds of ''Saponaria officinalis'' ...

Shiga toxin Shiga toxins are a family of related toxins with two major groups, Stx1 and Stx2, expressed by genes considered to be part of the genome of lambdoid prophages. The toxins are named after Kiyoshi Shiga, who first described the bacterial orig ...

*A ''

Spiroplasma ''Spiroplasma'' is a genus of Mollicutes, a group of small bacteria without cell walls. ''Spiroplasma'' shares the simple metabolism, parasitic lifestyle, fried-egg colony morphology and small genome of other ''Mollicutes'', but has a distinctive ...

'' toxin *

Trichosanthin Trichosanthin is a ribosome-inactivating protein. It is derived from ''Trichosanthes kirilowii''. It is also an abortifacient An abortifacient ("that which will cause a miscarriage" from Latin: ''abortus'' "miscarriage" and '' faciens'' "maki ...

* Viscumin (

European mistletoe ''Viscum album'' is a species of mistletoe in the family Santalaceae, commonly known as European mistletoe, common mistletoe or simply as mistletoe (Old English ''mistle''). It is native to Europe and western and southern Asia. ''Viscum album'' ...

) *

Pokeweed antiviral protein ''Phytolacca americana'', also known as American pokeweed, pokeweed, poke sallet, dragonberries, and inkberry, is a poisonous, herbaceous perennial plant in the pokeweed family Phytolaccaceae. This pokeweed grows . It has simple leaves on green ...

(

Phytolacca americana ''Phytolacca americana'', also known as American pokeweed, pokeweed, poke sallet, dragonberries, and inkberry, is a poisonous, herbaceous perennial plant in the pokeweed family Phytolaccaceae. This pokeweed grows . It has simple leaves on green ...

)

References

Protein domains {{Protein-stub