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

被引:109
作者
Blanchard, Bertrand [1 ,2 ]
Nurisso, Alessandra [1 ,2 ]
Hollville, Emilie [3 ]
Tetaud, Cecile [3 ]
Wiels, Joelle [3 ]
Pokorna, Martina [4 ,5 ]
Wimmerova, Michaela [4 ,5 ]
Varrot, Annabelle [1 ,2 ]
Imberty, Anne [1 ,2 ]
机构
[1] Univ Grenoble 1, CNRS, CERMAV, F-38041 Grenoble, France
[2] CNRS, CERMAV, ICMG, F-38041 Grenoble, France
[3] Univ Paris 11, CNRS, UMR 8126, Inst Gustave Roussy, F-94805 Villejuif, France
[4] Masaryk Univ, NCBR, CS-61137 Brno, Czech Republic
[5] Masaryk Univ, Dept Biochem, CS-61137 Brno, Czech Republic
关键词
lectin; glycosphingolipid; Pseudomonas aeruginosa; adhesion; oligosaccharides;
D O I
10.1016/j.jmb.2008.08.028
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The opportunistic pathogen Pseudomonas aeruginosa contains several carbohydrate-binding proteins, among which is the P. aeruginosa lectin I (PA-IL), which displays affinity for alpha-galactosylated glycans. Glycan arrays were screened and demonstrated stronger binding of PA-IL, toward alpha Gal1-4 beta Gal-terminating structures and weaker binding to alpha Gal1-3 beta Gal 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/p(k). Trisaccharide moieties of Gb3 (alpha Gal1-4 beta Gal1-4Glc) and isoglobotriaosyl-ceramide (alpha Gal1-3 beta Gal1-4Glc) were tested by titration microcalorimetry, and both displayed similar affinity to PA-IL in solution. The crystal structure of PA-IL complexed to alpha Gal1-3 beta Gal1-4Glc trisaccharide has been solved at 1.9-angstrom 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 alpha Gal1-3Gal with that toward alpha Gal1-4Gal. Docking studies demonstrated that alpha Gal1-4Gal 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. (C) 2008 Elsevier Ltd. All rights reserved.
引用
收藏
页码:837 / 853
页数:17
相关论文
共 64 条
  • [1] MOLECULAR MECHANICS - THE MM3 FORCE-FIELD FOR HYDROCARBONS .1.
    ALLINGER, NL
    YUH, YH
    LII, JH
    [J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1989, 111 (23) : 8551 - 8566
  • [2] AVICHEZER D, 1992, J BIOL CHEM, V267, P23023
  • [3] THE CCP4 SUITE - PROGRAMS FOR PROTEIN CRYSTALLOGRAPHY
    BAILEY, S
    [J]. ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, 1994, 50 : 760 - 763
  • [4] CYTOTOXICITY OF PSEUDOMONAS-AERUGINOSA INTERNAL LECTIN PA-I TO RESPIRATORY EPITHELIAL-CELLS IN PRIMARY CULTURE
    BAJOLETLAUDINAT, O
    GIRODDEBENTZMANN, S
    TOURNIER, JM
    MADOULET, C
    PLOTKOWSKI, MC
    CHIPPAUX, C
    PUCHELLE, E
    [J]. INFECTION AND IMMUNITY, 1994, 62 (10) : 4481 - 4487
  • [5] X-ray and molecular dynamics studies of concanavalin-A glucoside and mannoside complexes - Relating structure to thermodynamics of binding
    Bradbrook, GM
    Gleichmann, T
    Harrop, SJ
    Habash, J
    Raftery, J
    Kalb, J
    Yariv, J
    Hillier, IH
    Helliwell, JR
    [J]. JOURNAL OF THE CHEMICAL SOCIETY-FARADAY TRANSACTIONS, 1998, 94 (11): : 1603 - 1611
  • [6] FREE R-VALUE - A NOVEL STATISTICAL QUANTITY FOR ASSESSING THE ACCURACY OF CRYSTAL-STRUCTURES
    BRUNGER, AT
    [J]. NATURE, 1992, 355 (6359) : 472 - 475
  • [7] N-glycolyl GM1 ganglioside as a receptor for simian virus 40
    Campanero-Rhodes, Maria A.
    Smith, Alicia
    Chai, Wengang
    Sonnino, Sandro
    Mauri, Laura
    Childs, Robert A.
    Zhang, Yibing
    Ewers, Helge
    Helenius, Ari
    Imberty, Anne
    Feizi, Ten
    [J]. JOURNAL OF VIROLOGY, 2007, 81 (23) : 12846 - 12858
  • [8] Studies on the binding site of the galactose-specific agglutinin PA-IL from Pseudomonas aeruginosa
    Chen, CP
    Song, SC
    Gilboa-Garber, N
    Chang, KSS
    Wu, AM
    [J]. GLYCOBIOLOGY, 1998, 8 (01) : 7 - 16
  • [9] Structural basis of calcium and galactose recognition by the lectin PA-IL of Pseudomonas aeruginosa
    Cioci, G
    Mitchell, EP
    Gautier, C
    Wimmerová, M
    Sudakevitz, D
    Pérez, S
    Gilboa-Garber, N
    Imberty, A
    [J]. FEBS LETTERS, 2003, 555 (02) : 297 - 301
  • [10] VALIDATION OF THE GENERAL-PURPOSE TRIPOS 5.2 FORCE-FIELD
    CLARK, M
    CRAMER, RD
    VANOPDENBOSCH, N
    [J]. JOURNAL OF COMPUTATIONAL CHEMISTRY, 1989, 10 (08) : 982 - 1012