Ribotoxins

Ribotoxins are a subset of ribosome-targeting toxins—usually small, secreted proteins—that directly cleave a single phosphodiester bond within the sarcin-ricin loop of the 28S rRNA in eukaryotic ribosomes. This precise cleavage irreversibly inactivates the ribosome, effectively halting protein synthesis and leading to cell death if the toxin remains unneutralized.

Mechanism and action: Unlike many ribosome-inactivating proteins that depurinate rRNA, ribotoxins perform site-specific endoribonucleolytic cleavage within the sarcin-ricin loop. This action disrupts elongation factor binding and blocks translation. After cellular entry—often via endocytosis and trafficking to the cytosol—the ribotoxin acts directly on ribosomes, with effectiveness depending on delivery and concentration.

Structural and biological properties: Most ribotoxins are small, single-chain proteins, typically around 150 amino acids in length. They are produced by fungi and other microorganisms and function as endoribonucleases with high specificity for the SRL region of the large ribosomal RNA. Their compact structure and enzymatic activity underlie their potent cytotoxic effects.

Examples and scope: Alpha-sarcin is a prototypical ribotoxin, and restrictocin is another well-characterized member. Additional ribotoxins have been described in filamentous fungi and related organisms. While sharing the same general target (the ribosome), individual toxins differ in sequence, stability, and cellular uptake properties.

Applications and safety: In research, ribotoxins are used to study ribosome structure and function and as components in experimental cytotoxic or targeted delivery systems. Due to their high potency and potential for non-selective damage, handling is restricted to specialized laboratories and subject to strict safety regulations.