Cytotoxic ribosome-inactivating lectins from plants

Area of Science:

• Biochemistry
• Cell Biology
• Toxicology

Background:

• Ricin is a highly toxic heterodimeric plant lectin composed of a B-chain for cell binding and an A-chain for enzymatic activity.
• It inhibits protein synthesis by inactivating ribosomes, making it one of the most potent toxins known.

Purpose of the Study:

• To elucidate the intricate cellular pathway ricin utilizes to enter cells and reach its ribosomal substrate.
• To detail the molecular mechanisms of ricin's translocation into the cytosol and its subsequent ribosome inactivation.

Main Methods:

• The study outlines the multi-step process of ricin cell entry, including endocytosis, vesicular transport through the endomembrane system, and ER translocation.
• Key steps involve disulfide bond reduction, A-chain unfolding, Sec61p translocon-mediated translocation, and cytosolic refolding.

Main Results:

• Ricin binds to cell surface galactose residues via its B-chain (RTB) and is internalized through endocytosis.
• The ricin A-chain (RTA) translocates into the cytosol and enzymatically cleaves the sarcin-ricin domain of ribosomal RNA, leading to cell death.
• Ricin and related ribosome-inactivating proteins (RIPs) exhibit in vitro polynucleotide:adenosine glycosidase activity, with potential antiviral implications.

Conclusions:

• Ricin employs a complex, multi-compartmental pathway for cellular entry and ribosome inactivation.
• Understanding this pathway is crucial for developing strategies against ricin toxicity.
• The in vitro antiviral claims for RIPs require further in vivo validation.