Molecular Recognition of Complex-Type Biantennary N-Glycans by Protein Receptors: a Three-Dimensional View on Epitope Selection by NMR

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• 作者：Ana Ard谩 ; Pilar Blasco ; Daniel Var贸n Silva ; Volker Schubert ; Sabine Andr茅 ; Marta Bruix ; F. Javier Ca帽ada ; Hans-Joachim Gabius ; Carlo Unverzagt ; Jes煤s Jim茅nez-Barbero
• 刊名：The Journal of the American Chemical Society
• 出版年：2013
• 出版时间：February 20, 2013
• 年：2013
• 卷：135
• 期：7
• 页码：2667-2675
• 全文大小：525K
• 年卷期：v.135,no.7(February 20, 2013)
• ISSN：1520-5126

文摘

The current surge in defining glycobiomarkers by applying lectins rekindles interest in definition of the sugar-binding sites of lectins at high resolution. Natural complex-type N-glycans can present more than one potential binding motif, posing the question of the actual mode of interaction when interpreting, for example, lectin array data. By strategically combining N-glycan preparation with saturation-transfer difference NMR and modeling, we illustrate that epitope recognition depends on the structural context of both the sugar and the lectin (here, wheat germ agglutinin and a single hevein domain) and cannot always be predicted from simplified model systems studied in the solid state. We also monitor branch-end substitutions by this strategy and describe a three-dimensional structure that accounts for the accommodation of the 伪2,6-sialylated terminus of a biantennary N-glycan by viscumin. In addition, we provide a structural explanation for the role of terminal 伪2,6-sialylation in precluding the interaction of natural N-glycans with lectin from Maackia amurensis. The approach described is thus capable of pinpointing lectin-binding motifs in natural N-glycans and providing detailed structural explanations for lectin selectivity.