Structural Basis of the Preferential Binding for Globo-Series Glycosphingolipids Displayed by Pseudomonas aeruginosa Lectin I

Bertrand Blanchard, Alessandra Nurisso, Emilie Hollville, Cécile Tétaud, Joelle Wiels, Martina Pokorná, Michaela Wimmerová, Annabelle Varrot, Anne Imberty*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

121 Citations (Scopus)


The opportunistic pathogen Pseudomonas aeruginosa contains several carbohydrate-binding proteins, among which is the P. aeruginosa lectin I (PA-IL), which displays affinity for α-galactosylated glycans. Glycan arrays were screened and demonstrated stronger binding of PA-IL toward αGal1-4βGal-terminating structures and weaker binding to αGal1-3βGal ones in order to determine which human glycoconjugates could play a role in the carbohydrate-mediated adhesion of the bacteria. This was confirmed in vivo by testing the binding of the lectin to Burkitt lymphoma cells that present large amounts of globotriaosylceramide antigen Gb3/CD77/Pk. Trisaccharide moieties of Gb3 (αGal1-4βGal1-4Glc) and isoglobotriaosylceramide (αGal1-3βGal1-4Glc) were tested by titration microcalorimetry, and both displayed similar affinity to PA-IL in solution. The crystal structure of PA-IL complexed to αGal1-3βGal1-4Glc trisaccharide has been solved at 1.9-Ǻ resolution and revealed how the second galactose residue makes specific contacts with the protein surface. Molecular modeling studies were performed in order to compare the binding mode of PA-IL toward αGal1-3Gal with that toward αGal1-4Gal. Docking studies demonstrated that αGal1-4Gal creates another network of contacts for achieving a very similar affinity, and 10-ns molecular dynamics in explicit water allowed for analyzing the flexibility of each disaccharide ligand in the protein binding site. The higher affinity observed for binding to Gb3 epitope, both in vivo and on glycan array, is likely related to the presentation effect of the oligosaccharide on a surface, since only the Gb3 glycosphingolipid geometry is fully compatible with parallel insertion of neighboring trisaccharide heads in two binding sites of the same tetramer of PA-IL.

Original languageEnglish
Pages (from-to)837-853
Number of pages17
JournalJournal of Molecular Biology
Issue number4
Early online date22 Aug 2008
Publication statusPublished - 21 Nov 2008

Bibliographical note

Funding Information:
This work was supported by CNRS, the French Ministry of Research, the Ministry of Education of the Czech Republic (MSM0021622413), and the EEC European Community through programs MEST-CT-2004-503322 (CermavTrain) and MRTN-CT-2006-035546 (NODPERCEPTION). The glycan array resources were provided by the Consortium for Functional Glycomics through grant GM62116. Funds in support of this work from the Association pour la Recherche sur le Cancer (ARC 3454), the Association Vaincre la Mucoviscidose, and the GDR Pseudomonas are gratefully acknowledged. We also acknowledge the European Synchrotron Radiation Facility for access to synchrotron data collection facilities.


  • adhesion
  • glycosphingolipid
  • lectin
  • oligosaccharides
  • Pseudomonas aeruginosa


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