Unraveling functional significance of natural variations of a human galectin by glycodendrimersomes with programmable glycan surface

作者：Zhang Shaodong; Moussodia Ralph Olivier; Vertesy Sabine; Andre Sabine; Klein Michael L^*; Gabius Hans Joachim; Percec Virgil

来源：Proceedings of the National Academy of Sciences, 2015, 112(18): 5585-5590.

DOI：10.1073/pnas.1506220112

• adhesion
• agglutination
• glycobiology
• membrane mimic
• self-assembly

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 galectin8 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.

• 出版日期2015-5-5