Document Detail


Fatty acyl chains of Mycobacterium marinum lipooligosaccharides: structure, localization and acylation by PapA4 (MMAR_2343) protein.
MedLine Citation:
PMID:  21803773     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We have recently established the fine structure of the glycan backbone of lipooligosaccharides (LOS-I to LOS-IV) isolated from Mycobacterium marinum, a close relative of Mycobacterium tuberculosis. These studies culminated with the description of an unusual terminal N-acylated monosaccharide that confers important biological functions to LOS-IV, such as macrophage activation, that may be relevant to granuloma formation. It was, however, also suggested that the lipid moiety was required for LOSs to exert their immunomodulatory activity. Herein, using highly purified LOSs from M. marinum, we have determined through a combination of mass spectrometric and NMR techniques, the structure and localization of the fatty acids composing the lipid moiety. The occurrence of two distinct polymethyl-branched fatty acids presenting specific localizations is consistent with the presence of two highly related polyketide synthases (Pks5 and Pks5.1) in M. marinum and presumably involved in the synthesis of these fatty acyl chains. In addition, a bioinformatic search permitted us to identify a set of enzymes potentially involved in the biosynthesis or transfer of these lipids to the LOS trehalose unit. These include MMAR_2343, a member of the Pap (polyketide-associated protein) family, that acylates trehalose-based glycolipids in M. marinum. The participation of MMAR_2343 to LOS assembly was demonstrated using a M. marinum mutant carrying a transposon insertion in the MMAR_2343 gene. Disruption of MMAR_2343 resulted in a severe LOS breakdown, indicating that MMAR_2343, hereafter designated PapA4, fulfills the requirements for LOS acylation and assembly.
Authors:
Yoann Rombouts; Laeticia Alibaud; Séverine Carrère-Kremer; Emmanuel Maes; Caroline Tokarski; Elisabeth Elass; Laurent Kremer; Yann Guérardel
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-07-29
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  286     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-09-19     Completed Date:  2011-11-23     Revised Date:  2013-06-28    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  33678-88     Citation Subset:  IM    
Affiliation:
Université de Lille 1, Unité de Glycobiologie Structurale et Fonctionnelle, F-59650 Villeneuve d'Ascq, France.
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MeSH Terms
Descriptor/Qualifier:
Acylation
Amino Acid Sequence
Bacterial Proteins / metabolism*
Carbohydrate Conformation
Carbohydrate Sequence
Computational Biology
Fatty Acids / chemistry*,  metabolism*
Gas Chromatography-Mass Spectrometry
Gene Silencing
Genes, Bacterial / genetics
Lipopolysaccharides / chemistry*
Magnetic Resonance Spectroscopy
Molecular Sequence Data
Mycobacterium marinum / genetics,  metabolism*
Mycobacterium smegmatis / metabolism
Protons
Sequence Alignment
Trehalose / metabolism
Chemical
Reg. No./Substance:
0/Bacterial Proteins; 0/Fatty Acids; 0/Lipopolysaccharides; 0/Protons; 0/lipid-linked oligosaccharides; 99-20-7/Trehalose
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