Document Detail


Enzymatically inactive trans-sialidase from Trypanosoma cruzi binds sialyl and beta-galactopyranosyl residues in a sequential ordered mechanism.
MedLine Citation:
PMID:  14634017     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Host/parasite interaction mediated by carbohydrate/lectin recognition results in the attachment to and invasion of host cells and immunoregulation, enabling parasite replication and establishment of infection. Trypanosoma cruzi, the protozoan responsible for Chagas disease, expresses on its surface a family of enzymatically active and inactive trans-sialidases. The parasite uses the active trans-sialidase for glycoprotein sialylation in an unusual trans-glycosylation reaction. Inactive trans-sialidase is a sialic acid-binding lectin that costimulates host T cells through leucosialin (CD43) engagement. The co-mitogenic effect of trans-sialidase can be selectively abrogated by N-acetyllactosamine, suggesting the presence of an additional carbohydrate binding domain for galactosides, in addition to that for sialic acid. Here we investigated the interaction of inactive trans-sialidase in the presence of beta-galactosides. By using NMR spectroscopy, we demonstrate that inactive trans-sialidase has a beta-galactoside recognition site formed following a conformational switch induced by sialoside binding. Thus prior positioning of a sialyl residue is required for the beta-galactoside interaction. When an appropriate sialic acid-containing molecule is available, both sialoside and beta-galactoside are simultaneously accommodated in the inactive trans-sialidase binding pocket. This is the first report of a lectin recognizing two distinct ligands by a sequential ordered mechanism. This uncommon binding behavior may play an important role in several biological aspects of T. cruzi/host cell interaction and could shed more light into the catalytic mechanism of the sialic acid transfer reaction of enzymatically active trans-sialidase.
Authors:
Adriane R Todeschini; Wagner B Dias; Murielle F Girard; Jean-Michel Wieruszeski; Lucia Mendonça-Previato; Jose O Previato
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2003-11-21
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  279     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2004 Feb 
Date Detail:
Created Date:  2004-02-09     Completed Date:  2004-03-30     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:  5323-8     Citation Subset:  IM    
Affiliation:
Instituto de Biofísica Carlos Chagas Filho, Centro de Ciências da Saúde-Bloco G, Universidade Federal do Rio de Janeiro, 21 944970, Cidade Universitária, Ilha do Fundão, Rio de Janeiro, Brasil.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, CD*
Antigens, CD43
Binding Sites
Carbohydrate Sequence
Carbohydrates / chemistry
Chromatography
Galactose / chemistry*
Galactosides / chemistry
Glycoproteins
Lactose / chemistry
Ligands
Magnetic Resonance Spectroscopy
Models, Biological
N-Acetylneuraminic Acid / chemistry
Neuraminidase / chemistry*
Protein Binding
Protein Structure, Tertiary
Sepharose / chemistry
Sialoglycoproteins / metabolism
T-Lymphocytes / metabolism
Trypanosoma cruzi / enzymology*
Chemical
Reg. No./Substance:
0/Antigens, CD; 0/Antigens, CD43; 0/Carbohydrates; 0/Galactosides; 0/Glycoproteins; 0/Ligands; 0/Sialoglycoproteins; 0/beta-galactoside; 131-48-6/N-Acetylneuraminic Acid; 26566-61-0/Galactose; 63-42-3/Lactose; 9012-36-6/Sepharose; EC 3.2.1.-/trans-sialidase; EC 3.2.1.18/Neuraminidase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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