Ribosome-inactivating protein

A ribosome-inactivating protein (RIP) is a protein synthesis inhibitor that acts at the ribosome.[2]

Ribosome-inactivating protein
Structure of pokeweed antiviral protein.[1]
Identifiers
Symbol	RIP
Pfam	PF00161
InterPro	IPR001574
PROSITE	PDOC00248
SCOPe	1paf / SUPFAM
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary PDB PDB: 1abr​ PDB: 1aha​ PDB: 1ahb​ PDB: 1ahc​ PDB: 1apa​ PDB: 1apg​ PDB: 1br5​ PDB: 1br6​ PDB: 1bry​ PDB: 1cf5​

A number of bacterial and plant toxins act by inhibiting protein synthesis in eukaryotic cells. The toxins of the Shiga and ricin family inactivate 60S ribosomal subunits by an N-glycosidic cleavage, which releases a specific adenine base from the sugar-phosphate backbone of 28S rRNA.[3][4][5] Members of the family include shiga and shiga-like toxins, and type I (e.g. trichosanthin and luffin) and type II (e.g. ricin, agglutinin, and abrin) 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 immunotoxins to treat cancers. Further, trichosanthin has been shown to have potent activity against HIV-1-infected T cells and macrophages.[6] 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;[7] this lies near a conserved arginine, which also plays a role in catalysis.[8]

Examples include:

• Abrin
• Beetin
• Ricin
• Saporin
• Shiga toxin
• Spiroplasma proteins[9]
• Trichosanthin
• Viscumin (European mistletoe)
• Pokeweed antiviral protein (Phytolacca americana)[10]

Ribosome-inactivating proteins (RIPs) are separated into three types based on protein domain composition:

• Type I: RIPs-I are polypeptides composed of an A domain. This is the site of N-glycosidase activity.
• Type II: RIPs-II are composed of an A domain with similar catalytic activity to Type I RIPs, and a B domain with lectin-binding properties. These properties facilitate entry into the cell, thus making Type II particularly cytotoxic. The A and B domains are fused together by disulfide bonds.[11]
  • RIPs-II are considered potent toxins. The B domain is able to bind galactosyl moieties on the cell surface which facilitates entry into the cell, where the A domain can perform its catalytic activity on 28S rRNA in the cytosol.[12]
• Type III: RIPs-III are separated into two subgroups. One subgroup contains the same original RIP domain (A), and a C-terminal with unknown functionality. The other subgroup is similar to Type I, but contains a site for inactivation.[11]

They exist in bacteria and plants.[13]

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.