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标题：Unraveling functional significance of natural variations of a human galectin by glycodendrimersomes with programmable glycan surface
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作者：Shaodong Zhang ; Ralph-Olivier Moussodia ; Sabine Vértesy 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2015
卷号：112
期号：18
页码：5585-5590
DOI：10.1073/pnas.1506220112
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceLectins are endogenous sugar receptors involved in diverse physiological and disease-associated processes. The functional consequences of naturally occurring single-nucleotide polymorphism and alternative splicing in lectins has been explored using glycodendrimersomes, a versatile test system with programmable glycan (complex carbohydrates) display. Importantly, glycodendrimersomes facilitate quantitative determination of lectin-mediated cross-linking, a hallmark of their activity. Threshold and kinetic effects measured for a human galectin associated with autoimmune disease document the sensitivity of the test system and highlight its potential as a new and highly versatile supramolecular sensor for biomedical applications. 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.
关键词：adhesion ; agglutination ; glycobiology ; membrane mimic ; self-assembly