Structural basis for oligosaccharide-mediated adhesion of Pseudomonas aeruginosa in the lungs of cystic fibrosis patients.
Pseudomonas aeruginosa galactose- and fucose-binding lectins (PA-IL and PA-IIL) contribute to the virulence of this pathogenic bacterium, which is a major cause of morbidity and mortality in cystic fibrosis patients. The crystal structure of PA-IIL in complex with fucose reveals a tetrameric structure. Each monomer displays a nine-stranded, antiparallel b-sandwich arrangement and contains two close calcium cations that mediate the binding of fucose in a recognition mode unique among carbohydrate-protein interactions. Experimental binding studies, together with theoretical docking of fucose-containing oligosaccharides, are consistent with the assumption that antigens of the Lewis a (Le(a)) series may be the preferred ligands of this lectin. Precise knowledge of the lectin-binding site should allow a better design of new antibacterial-adhesion prophylactics.
Mitchell
Edward
E
E.S.R.F. Experiments Division, BP 220, F-38043 Grenoble cedex, France.
Houles
Corinne
C
Sudakevitz
Dvora
D
Wimmerova
Michaela
M
Gautier
Catherine
C
Pérez
Serge
S
Wu
Albert M
AM
Gilboa-Garber
Nechama
N
Imberty
Anne
A
D018829:Adhesins, Bacterial / Q000737:chemistry* / Q000378:metabolism; D001422:Bacterial Adhesion; D001665:Binding Sites; D002118:Calcium / Q000737:chemistry / Q000378:metabolism; D018360:Crystallography, X-Ray; D003550:Cystic Fibrosis / Q000382:microbiology; D005643:Fucose / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D037102:Lectins / Q000737:chemistry* / Q000378:metabolism; D008168:Lung / Q000382:microbiology; D046911:Macromolecular Substances; D008958:Models, Molecular; D009844:Oligosaccharides / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011550:Pseudomonas aeruginosa / Q000472:pathogenicity*
D018829:Adhesins, Bacterial; D037102:Lectins; D046911:Macromolecular Substances; D009844:Oligosaccharides; C038692:adhesin, Pseudomonas; D005643:Fucose; D002118:Calcium