LppX is a lipoprotein required for the translocation of phthiocerol dimycocerosates to the surface of Mycobacterium tuberculosis

• Published in: The EMBO journal Vol. 25; no. 7; pp. 1436 - 1444
• Main Authors: Sulzenbacher, Gerlind, Canaan, Stéphane, Bordat, Yann, Neyrolles, Olivier, Stadthagen, Gustavo, Roig-Zamboni, Véronique, Rauzier, Jean, Maurin, Damien, Laval, Françoise, Daffé, Mamadou, Cambillau, Christian, Gicquel, Brigitte, Bourne, Yves, Jackson, Mary
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 05.04.2006; Blackwell Publishing Ltd; EMBO Press
• Subjects: Animals; Bacteria; Biological Transport; Cell Membrane - metabolism; Complex lipids; crystallography; Crystallography, X-Ray; Female; Hydrophobic and Hydrophilic Interactions; Life Sciences; Lipids; Lipids - chemistry; Lipids - physiology; lipoprotein; Lipoproteins - chemistry; Lipoproteins - genetics; Lipoproteins - physiology; Lung - virology; Membranes; Mice; Mice, Inbred BALB C; Models, Molecular; Molecular biology; Mutation; Mycobacterium; Mycobacterium tuberculosis; Mycobacterium tuberculosis - genetics; Mycobacterium tuberculosis - metabolism; Mycobacterium tuberculosis - pathogenicity; Pathogens; phthiocerol dimycocerosates; Protein Conformation; Protein Folding; Proteins; Translocation; Tuberculosis; Tuberculosis, Pulmonary - virology; Virulence; Mycobacterium; crystallography; phthiocerol dimycocerosates; lipoprotein; tuberculosis
• ISSN: 0261-4189; 1460-2075
• DOI: 10.1038/sj.emboj.7601048

Cell envelope lipids play an important role in the pathogenicity of mycobacteria, but the mechanisms by which they are transported to the outer membrane of these prokaryotes are largely unknown. Here, we provide evidence that LppX is a lipoprotein required for the translocation of complex lipids, the phthiocerol dimycocerosates (DIM), to the outer membrane of Mycobacterium tuberculosis. Abolition of DIM transport following disruption of the lppX gene is accompanied by an important attenuation of the virulence of the tubercle bacillus. The crystal structure of LppX unveils an U‐shaped β‐half‐barrel dominated by a large hydrophobic cavity suitable to accommodate a single DIM molecule. LppX shares a similar fold with the periplasmic molecular chaperone LolA and the outer membrane lipoprotein LolB, which are involved in the localization of lipoproteins to the outer membrane of Gram‐negative bacteria. Based on the structure and although an indirect participation of LppX in DIM transport cannot yet be ruled out, we propose LppX to be the first characterized member of a family of structurally related lipoproteins that carry lipophilic molecules across the mycobacterial cell envelope.