Soares Cátia Oliveira, Grosso Ana Sofia, Ereño-Orbea June, Coelho Helena, Marcelo Filipa
Associate Laboratory i4HB-Institute for Health and Bioeconomy, NOVA School of Science and Technology, NOVA University Lisbon, Caparica, Portugal.
Department of Chemistry, UCIBIO-Applied Molecular Biosciences Unit, NOVA School of Science and Technology, NOVA University Lisbon, Caparica, Portugal.
Front Mol Biosci. 2021 Nov 15;8:727847. doi: 10.3389/fmolb.2021.727847. eCollection 2021.
All cells are decorated with a highly dense and complex structure of glycan chains, which are mostly attached to proteins and lipids. In this context, sialic acids are a family of nine-carbon acidic monosaccharides typically found at the terminal position of glycan chains, modulating several physiological and pathological processes. Sialic acids have many structural and modulatory roles due to their negative charge and hydrophilicity. In addition, the recognition of sialic acid glycans by mammalian cell lectins, such as siglecs, has been described as an important immunological checkpoint. Furthermore, sialic acid glycans also play a pivotal role in host-pathogen interactions. Various pathogen receptors exposed on the surface of viruses and bacteria are responsible for the binding to sialic acid sugars located on the surface of host cells, becoming a critical point of contact in the infection process. Understanding the molecular mechanism of sialic acid glycans recognition by sialic acid-binding proteins, present on the surface of pathogens or human cells, is essential to realize the biological mechanism of these events and paves the way for the rational development of strategies to modulate sialic acid-protein interactions in diseases. In this perspective, nuclear magnetic resonance (NMR) spectroscopy, assisted with molecular modeling protocols, is a versatile and powerful technique to investigate the structural and dynamic aspects of glycoconjugates and their interactions in solution at the atomic level. NMR provides the corresponding ligand and protein epitopes, essential for designing and developing potential glycan-based therapies. In this review, we critically discuss the current state of knowledge about the structural features behind the molecular recognition of sialic acid glycans by different receptors, naturally present on human cells or pathogens, disclosed by NMR spectroscopy and molecular modeling protocols.
所有细胞都装饰有高度密集且复杂的聚糖链结构，这些聚糖链大多附着于蛋白质和脂质上。在这种情况下，唾液酸是一类九碳酸性单糖，通常位于聚糖链的末端位置，调节多种生理和病理过程。由于其负电荷和亲水性，唾液酸具有许多结构和调节作用。此外，哺乳动物细胞凝集素（如唾液酸结合免疫球蛋白样凝集素）对唾液酸聚糖的识别已被描述为一个重要的免疫检查点。此外，唾液酸聚糖在宿主 - 病原体相互作用中也起着关键作用。病毒和细菌表面暴露的各种病原体受体负责与宿主细胞表面的唾液酸糖结合，成为感染过程中的一个关键点。了解病原体或人类细胞表面存在的唾液酸结合蛋白对唾液酸聚糖的识别分子机制，对于认识这些事件的生物学机制至关重要，并为合理开发调节疾病中唾液酸 - 蛋白质相互作用的策略铺平了道路。从这个角度来看，核磁共振（NMR）光谱结合分子建模方案，是一种通用且强大的技术，可在原子水平上研究糖缀合物的结构和动力学方面及其在溶液中的相互作用。NMR提供了相应的配体和蛋白质表位，这对于设计和开发潜在的基于聚糖的疗法至关重要。在这篇综述中，我们批判性地讨论了通过NMR光谱和分子建模方案揭示的、关于人类细胞或病原体天然存在的不同受体对唾液酸聚糖分子识别背后结构特征的当前知识状态。
