Document Detail


Identification of the ricin lipase site and implication in cytotoxicity.
MedLine Citation:
PMID:  12611897     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Juliette Morlon-Guyot; Mohamed Helmy; Sophie Lombard-Frasca; David Pignol; Gérard Piéroni; Bruno Beaumelle
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2003-02-28
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  278     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2003 May 
Date Detail:
Created Date:  2003-05-05     Completed Date:  2003-06-30     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  17006-11     Citation Subset:  IM    
Affiliation:
UMR 5539 CNRS, Département Biologie-Santé, Université Montpellier II, 34095 Montpellier, France.
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MeSH Terms
Descriptor/Qualifier:
Enzyme Activation
Kinetics
Lipase / analysis*,  chemistry,  metabolism
Models, Molecular
Protein Conformation
Protein Subunits
Ricin / analysis*,  chemistry,  metabolism
Chemical
Reg. No./Substance:
0/Protein Subunits; 9009-86-3/Ricin; EC 3.1.1.3/Lipase

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