How Ricin Reaches its Target in the Cytosol of Mammalian Cells

The cytotoxic plant protein ricin comprises a lectin B chain that binds promiscuously to glycolipids and glycoproteins at the surface of mammalian cells, disulphide-coupled to a toxic A chain which depurinates target ribosomes. To find these cytosolic targets, the A chain has to cross a biological membrane, which is not a simple task for a folded protein. The secretory pathway of eukaryotic cells is reversible and ricin can take advantage of this to move from the plasma membrane, via the Golgi, to the ER whose membrane is crossed to gain access to the cytosol. Since membrane traversal is preceded by an unfolding step, there is a clear requirement for cytosolic re-folding of ricin to gain a catalytic conformation. This final step for ricin is accomplished after triage by cytosolic chaperones, underlining the central role of these in cellular protein folding