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. 2015 May 5;112(18):5585-90.
doi: 10.1073/pnas.1506220112. Epub 2015 Apr 20.

Unraveling Functional Significance of Natural Variations of a Human Galectin by Glycodendrimersomes With Programmable Glycan Surface

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Free PMC article

Unraveling Functional Significance of Natural Variations of a Human Galectin by Glycodendrimersomes With Programmable Glycan Surface

Shaodong Zhang et al. Proc Natl Acad Sci U S A. .
Free PMC article

Abstract

Surface-presented glycans (complex carbohydrates) are docking sites for adhesion/growth-regulatory galectins within cell-cell/matrix interactions. Alteration of the linker length in human galectin-8 and single-site mutation (F19Y) are used herein to illustrate the potential of glycodendrimersomes with programmable glycan displays as a model system to reveal the functional impact of natural sequence variations in trans recognition. Extension of the linker length slightly reduces lectin capacity as agglutinin and slows down aggregate formation at low ligand surface density. The mutant protein is considerably less active as agglutinin and less sensitive to low-level ligand presentation. The present results suggest that mimicking glycan complexity and microdomain occurrence on the glycodendrimersome surface can provide key insights into mechanisms to accomplish natural selectivity and specificity of lectins in structural and topological terms.

Keywords: adhesion; agglutination; glycobiology; membrane mimic; self-assembly.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1.
Fig. 1.
The different physiological forms of hGal-8 differing in linker length (hGal-8L and hGal-8S) and presence of a single-site sequence deviation at position 19 (labeled by an asterisk). Schematic of the architectures of the proteins with two different carbohydrate recognition domains (A), their fold (B), and sequences (C). Arrows in B denote site of contact for the ligand (galactose)
Fig. 2.
Fig. 2.
Agglutination assays between hGal-8S (2 mg⋅mL−1 in 100 μL of PBS) and Lac-containing glycodendrimersomes (mmol⋅L−1 in 900 μL of PBS) of different topological modes to present the binding partner for the lectin.
Fig. 3.
Fig. 3.
Agglutination assays between twin-mixed Lac-presenting (Lac) glycodendrimersomes (0.2 mmol⋅L−1 in 900 μL of PBS) and hGal-8 with solely C or N domain or mixture of the C + N domains (2.0 mg⋅mL−1 in 100 μL of PBS).
Fig. 4.
Fig. 4.
Agglutination assays between hGal-8S (2 mg⋅mL−1 in 100 μL of PBS) and mixtures of twin-mixed Man-containing (Man) and Lac-containing (Lac) glycodendrimersomes to produce different surface compositions (Man + Lac = 0.2 mmol⋅L−1 in 900 μL of PBS).
Fig. 5.
Fig. 5.
Agglutination assays between hGal-8L (2 mg⋅mL−1 in 100 μL of PBS) and mixtures of twin-mixed Man-containing (Man) and Lac-containing (Lac) glycodendrimersomes to produce different surface compositions (Man + Lac = 0.2 mmol⋅L−1 in 900 μL of PBS) for 1,500 s (A) and 8,000 s (B).
Fig. 6.
Fig. 6.
Agglutination assays between CG-8S (2 mg⋅mL−1 in 100 μL of PBS) and mixtures of twin-mixed Man-containing (Man) and Lac-containing (Lac) glycodendrimersomes to produce different surface compositions (Man + Lac = 0.2 mmol⋅L−1 in 900 μL of PBS).

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