Carbohydrate–Lectin Interactions: An Unexpected Contribution to Affinity

Navarra, Giulio; Zihlmann, Pascal; Jakob, R.P.; Stangier, Katja; Preston, Roland C.; Rabbani, Said; Smieško, Martin; Wagner, Bea; Maier, Timm; Ernst, Beat

doi:10.1002/cbic.201600615

Cited by 11 publications

(7 citation statements)

References 46 publications

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“…Conversely, these termini locally influenced the conformation of neighboring surface loops, but this did not reach or alter the binding site functionality, as confirmed by ITC measurements. The latest revealed a correlation between gain in affinity and oligosaccharide length that is not uncommon for bacterial lectins but remains to be fully clarified [23]. As is usually observed for lectin-carbohydrate pairs, the interaction was driven by enthalpy, with unfavorable entropy.…”

Section: Discussionmentioning

confidence: 86%

BC2L-C N-Terminal Lectin Domain Complexed with Histo Blood Group Oligosaccharides Provides New Structural Information

2020

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Lectins mediate adhesion of pathogens to host tissues, filling in a key role in the first steps of infection. Belonging to the opportunistic pathogen Burkholderia cenocepacia, BC2L-C is a superlectin with dual carbohydrate specificity, believed to mediate cross-linking between bacteria and host cells. Its C-terminal domain binds to bacterial mannosides while its N-terminal domain (BCL2-CN) recognizes fucosylated human epitopes. BC2L-CN presents a tumor necrosis factor alpha (TNF-α) fold previously unseen in lectins with a novel fucose binding mode. We report, here, the production of a novel recombinant form of BC2L-CN (rBC2L-CN2), which allowed better protein stability and unprecedented co-crystallization with oligosaccharides. Isothermal calorimetry measurements showed no detrimental effect on ligand binding and data were obtained on the binding of Globo H hexasaccharide and l-galactose. Crystal structures of rBC2L-CN2 were solved in complex with two blood group antigens: H-type 1 and H-type 3 (Globo H) by X-ray crystallography. They provide new structural information on the binding site, of importance for the structural-based design of glycodrugs as new antimicrobials with antiadhesive properties.

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Section: Discussionmentioning

confidence: 86%

BC2L-C N-Terminal Lectin Domain Complexed with Histo Blood Group Oligosaccharides Provides New Structural Information

2020

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“… c αGal14Gal disaccharide, determined as IC50 by fluorescence polarization ( Beshr et al, 2017 ). d αGal14Gal disaccharide, determined by ITC ( Navarra et al, 2017 ). e αGal14Gal disaccharide, determined by ITC ( Zhang et al, 2016 ).…”

Section: Diversity Structural Organization and Binding Mechanisms Of Gb3-binding Lectinsmentioning

confidence: 99%

Structural Diversities of Lectins Binding to the Glycosphingolipid Gb3

Siukstaite

Imberty

Römer

2021

Front. Mol. Biosci.

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Glycolipids are present on the surfaces of all living cells and thereby represent targets for many protein receptors, such as lectins. Understanding the interactions between lectins and glycolipids is essential for investigating the functions of lectins and the dynamics of glycolipids in living membranes. This review focuses on lectins binding to the glycosphingolipid globotriaosylceramide (Gb3), an attractive host cell receptor, particularly for pathogens and pathogenic products. Shiga toxin (Stx), from Shigella dysenteriae or Escherichia coli, which is one of the most virulent bacterial toxins, binds and clusters Gb3, leading to local negative membrane curvature and the formation of tubular plasma membrane invaginations as the initial step for clathrin-independent endocytosis. After internalization, it is embracing the retrograde transport pathway. In comparison, the homotetrameric lectin LecA from Pseudomonas aeruginosa can also bind to Gb3, triggering the so-called lipid zipper mechanism, which results in membrane engulfment of the bacterium as an important step for its cellular uptake. Notably, both lectins bind to Gb3 but induce distinct plasma membrane domains and exploit mainly different transport pathways. Not only, several other Gb3-binding lectins have been described from bacterial origins, such as the adhesins SadP (from Streptococcus suis) and PapG (from E. coli), but also from animal, fungal, or plant origins. The variety of amino acid sequences and folds demonstrates the structural versatilities of Gb3-binding lectins and asks the question of the evolution of specificity and carbohydrate recognition in different kingdoms of life.

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“…Si WSC3 binds β ‐glucan with a K d value of 12.5 μM ± 8.8 μM and a molar ratio of protein to substrate of 1 : 3. Although the affinity of WSC3 to β ‐glucan is lower compared to the K d value of ~100 nM for the native Si FGB1 (Wawra et al ., ) this is still a strong binding affinity as many lectins bind in the millimolar range (Navarra et al ., ). Our data show that the higher affinity of Si WSC3 for longer carbohydrate polymers most likely requires a complex 3D polysaccharide structure.…”

Section: Discussionmentioning

confidence: 97%

FGB1 and WSC3 are in planta‐induced β‐glucan‐binding fungal lectins with different functions

et al. 2019

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Summary In the root endophyte Serendipita indica, several lectin‐like members of the expanded multigene family of WSC proteins are transcriptionally induced in planta and are potentially involved in β‐glucan remodeling at the fungal cell wall. Using biochemical and cytological approaches we show that one of these lectins, SiWSC3 with three WSC domains, is an integral fungal cell wall component that binds to long‐chain β1‐3‐glucan but has no affinity for shorter β1‐3‐ or β1‐6‐linked glucose oligomers. Comparative analysis with the previously identified β‐glucan‐binding lectin SiFGB1 demonstrated that whereas SiWSC3 does not require β1‐6‐linked glucose for efficient binding to branched β1‐3‐glucan, SiFGB1 does. In contrast to SiFGB1, the multivalent SiWSC3 lectin can efficiently agglutinate fungal cells and is additionally induced during fungus–fungus confrontation, suggesting different functions for these two β‐glucan‐binding lectins. Our results highlight the importance of the β‐glucan cell wall component in plant–fungus interactions and the potential of β‐glucan‐binding lectins as specific detection tools for fungi in vivo.

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Carbohydrate–Lectin Interactions: An Unexpected Contribution to Affinity

Cited by 11 publications

References 46 publications

BC2L-C N-Terminal Lectin Domain Complexed with Histo Blood Group Oligosaccharides Provides New Structural Information

BC2L-C N-Terminal Lectin Domain Complexed with Histo Blood Group Oligosaccharides Provides New Structural Information

Structural Diversities of Lectins Binding to the Glycosphingolipid Gb3

FGB1 and WSC3 are in planta‐induced β‐glucan‐binding fungal lectins with different functions

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