From Surf Wiki (app.surf) — the open knowledge base

Ribosome-inactivating protein

Protein synthesis inhibitor

Field	Value
Symbol	RIP
Name	Ribosome-inactivating protein
image	PDB 1paf EBI.jpg
caption	Structure of pokeweed antiviral protein.
Pfam	PF00161
InterPro	IPR001574
PROSITE	PDOC00248
SCOP	1paf
PDB

A ribosome-inactivating protein (RIP) is a protein synthesis inhibitor that acts at the eukaryotic ribosome. This protein family 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 base from the sugar-phosphate backbone of 28S rRNA. RIPs exist in bacteria and plants.

Members of the family include shiga 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. 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 residue, 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.

Structural Similarities among RIPs. Original figure can be found in <ref>Legler PM, et al. Textbooks of Military Medicine, Medical Aspects of Biological Warfare, 2018, Borden Institute, Chap 16: Ricin, Page 273-401</ref>

Classification

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 structure and catalytic activity to Type I RIPs, and a new 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.
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.
Shiga toxin belongs to its own group, as the carbohydrate-binding ability (B5 domain) evolved separately and the catalytic domain is closer to type I (A) RIPs than to type II (AB).

Examples

Examples include:

Type A: Plant antiviral proteins (Beetin, Saporin, Pokeweed antiviral protein (Phytolacca americana), Trichosanthin), a Spiroplasma toxin
Type AB: Abrin, Ricin, Viscumin (European mistletoe)
Type AC:
Type AD:
Shiga toxin

References

(October 1993). "The 2.5 A structure of pokeweed antiviral protein". Journal of Molecular Biology.
{{MeSH name. Ribosome+Inactivating+Proteins
(January 1988). "Site of action of a Vero toxin (VT2) from Escherichia coli O157:H7 and of Shiga toxin on eukaryotic ribosomes. RNA N-glycosidase activity of the toxins". European Journal of Biochemistry.
(January 1989). "Ribosome inactivation by ricin A chain: a sensitive method to assess the activity of wild-type and mutant polypeptides". The EMBO Journal.
(1991). "Conserved amino acid residues in ribosome-inactivating proteins from plants". Biochimie.
(2007). "Structure-function study of maize ribosome-inactivating protein: implications for the internal inactivation region and the sole glutamate in the active site". Nucleic Acids Research.
(May 1994). "Structure of trichosanthin at 1.88 A resolution". Proteins.
(April 1988). "Evidence that glutamic acid 167 is an active-site residue of Shiga-like toxin I". Proceedings of the National Academy of Sciences of the United States of America.
(October 1993). "The 2.5 A structure of pokeweed antiviral protein". Journal of Molecular Biology.
(9 February 2018). "The Plant Ribosome-Inactivating Proteins Play Important Roles in Defense against Pathogens and Insect Pest Attacks". Frontiers in Plant Science.
Legler PM, et al. Textbooks of Military Medicine, Medical Aspects of Biological Warfare, 2018, Borden Institute, Chap 16: Ricin, Page 273-401
(December 2014). "Identification of RIP-II Toxins by Affinity Enrichment, Enzymatic Digestion and LC-MS". Analytical Chemistry.
(September 2017). "Ribosome Inactivating Proteins from an evolutionary perspective". Toxicon.
(January 2015). "Pokeweed antiviral protein, a ribosome inactivating protein: activity, inhibition and prospects". Toxins.
(January 2016). "A ribosome-inactivating protein in a Drosophila defensive symbiont". Proceedings of the National Academy of Sciences of the United States of America.

Info: Wikipedia Source

This article was imported from Wikipedia and is available under the Creative Commons Attribution-ShareAlike 4.0 License. Content has been adapted to SurfDoc format. Original contributors can be found on the article history page.

ribosome-inactivating-proteins protein-domains

Want to explore this topic further?

Ask Mako anything about Ribosome-inactivating protein — get instant answers, deeper analysis, and related topics.

Research with Mako

Free with your Surf account

Content sourced from Wikipedia, available under CC BY-SA 4.0.

This content may have been generated or modified by AI. CloudSurf Software LLC is not responsible for the accuracy, completeness, or reliability of AI-generated content. Always verify important information from primary sources.

Report