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Article Dans Une Revue Journal of Biological Chemistry Année : 2003

Identification of the Ricin Lipase Site and Implication in Cytotoxicity

Résumé

Ricin is a heterodimeric plant toxin and the prototype of type II ribosome-inactivating proteins. Its B-chain is a lectin that enables cell binding. After endocytosis, the A-chain translocates through the membrane of intracellular compartments to reach the cytosol where its N-glycosidase activity inactivates ribosomes, thereby arresting protein synthesis. We here show that ricin possesses a functional lipase active site at the interface between the two subunits. It involves residues from both chains. Mutation to alanine of catalytic serine 221 on the A-chain abolished ricin lipase activity. Moreover, this mutation slowed down the A-chain translocation rate and inhibited toxicity by 35%. Lipase activity is therefore required for efficient ricin A-chain translocation and cytotoxicity. This conclusion was further supported by structural examination of type II ribosome-inactivating proteins that showed that this lipase site is present in toxic (ricin and abrin) but is altered in nontoxic (ebulin 1 and mistletoe lectin I) members of this family.
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Dates et versions

hal-02998151 , version 1 (10-11-2020)

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Juliette Morlon-Guyot, Mohamed Helmy, Sophie Lombard-Frasca, David Pignol, Gérard Pieroni, et al.. Identification of the Ricin Lipase Site and Implication in Cytotoxicity. Journal of Biological Chemistry, 2003, 278 (19), pp.17006-17011. ⟨10.1074/jbc.M209516200⟩. ⟨hal-02998151⟩
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