LppX is a lipoprotein required for the translocation of phthiocerol dimycocerosates to the surface of Mycobacterium tuberculosis.
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 beta-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.
AFMB, CNRS UMR 6098, Marseille Cedex, France.
Gerlind
G
Sulzenbacher
Stéphane
S
Canaan
Yann
Y
Bordat
Olivier
O
Neyrolles
Gustavo
G
Stadthagen
Véronique
V
Roig-Zamboni
Jean
J
Rauzier
Damien
D
Maurin
Françoise
F
Laval
Mamadou
M
Daffé
Christian
C
Cambillau
Brigitte
B
Gicquel
Yves
Y
Bourne
Mary
M
Jackson
D000818:Animals; D001692:Biological Transport; D002462:Cell Membrane / Q000378:metabolism; D018360:Crystallography, X-Ray; D005260:Female; D057927:Hydrophobic and Hydrophilic Interactions; D008055:Lipids / Q000737:chemistry / Q000502:physiology*; D008074:Lipoproteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D008168:Lung / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D011487:Protein Conformation; D017510:Protein Folding; D014397:Tuberculosis, Pulmonary / Q000821:virology; D014774:Virulence
D008055:Lipids; D008074:Lipoproteins; C008901:phthiocerol dimycocerosate