Glycobiology最新文献

Protein engineering strategies to develop lectins by design. 设计开发凝集素的蛋白质工程策略。

IF 3.4 3区生物学

Glycobiology Pub Date : 2025-07-22 DOI: 10.1093/glycob/cwaf041

Ryoma Hombu, Lauren E Beatty, Sriram Neelamegham

{"title":"Protein engineering strategies to develop lectins by design.","authors":"Ryoma Hombu, Lauren E Beatty, Sriram Neelamegham","doi":"10.1093/glycob/cwaf041","DOIUrl":"https://doi.org/10.1093/glycob/cwaf041","url":null,"abstract":"Glycans regulate a wide array of biological processes, making them central to studies of cell biology. Thus, it is essential to characterize the spatiotemporal dynamics of glycans on cells and tissues, and to elucidate how glycan structures affect protein and cell function. Among the available molecular tools, glycan-binding proteins (GBPs), including naturally occurring lectins, are uniquely suited to provide this information at single-cell resolution. However, the diversity of cell-surface glycans far exceeds the number of readily available GBPs. Moreover, conventional lectins often possess shallow binding pockets that limit their recognition to terminal glycan epitopes, and such recognition often proceeds with low binding affinity. Protein engineering offers a promising strategy to expand GBP specificity, enhance affinity, and introduce novel binding capabilities. Currently large gaps remain between the available protein design principles and their application to GBP engineering. This has somewhat slowed progress in the development of glycan-targeted tools. In this review, we outline recent efforts that use rational design to inform GBP engineering for specific tasks. We also present methods to select suitable protein scaffolds and the application of directed evolution for optimizing lectin design. This includes our recent efforts to modify glycosyltransferases into GBPs, which potentially offers a predictive strategy to design lectins based on desired properties. Together, the presentation offers a roadmap for developing next-generation glycan binding proteins capable of decoding the complex glycan landscape of cells.","PeriodicalId":12766,"journal":{"name":"Glycobiology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144690027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A synthetic HS structure selectively impairs the morphology and function of excitatory synapse by disrupting neurexin1 interactions. 合成的HS结构通过破坏神经蛋白1的相互作用选择性地损害兴奋性突触的形态和功能。

IF 3.4 3区生物学

Glycobiology Pub Date : 2025-06-23 DOI: 10.1093/glycob/cwaf039

Qin Xu, Leanne Auyeung, Zhangjie Wang, Yongmei Xu, Jian Liu, Peng Zhang

{"title":"A synthetic HS structure selectively impairs the morphology and function of excitatory synapse by disrupting neurexin1 interactions.","authors":"Qin Xu, Leanne Auyeung, Zhangjie Wang, Yongmei Xu, Jian Liu, Peng Zhang","doi":"10.1093/glycob/cwaf039","DOIUrl":"10.1093/glycob/cwaf039","url":null,"abstract":"Excitatory and inhibitory synapses are the two major fundamental units of neuronal communication in the brain. The imbalance between excitatory and inhibitory synapses (E/I imbalance) is a leading mechanism underlying mental illness. Heparan sulfate (HS), a complex polysaccharide frequently implicated in mental disorders, is an emergent player in synaptic function. Yet, it remains unclear whether and how HS plays a preferential role in excitatory versus inhibitory synapses. This question is further complicated by the structural complexity of HS and the combined effects of both HS glycans and their attached proteoglycans. To address this challenge, we developed a platform that combines synthetic chemistry and synaptic biology to dissect the role of pure HS glycans in synapse development. As proof of principle, we assessed the effects of a synthetic dodecasaccharide (12-mer-19) and its non-sulfated counterpart (12-mer-NAc) on excitatory and inhibitory synapses in primary rat hippocampal neuron cultures. Unexpectedly, we found that 12-mer-19 selectively impaired the morphology and function of excitatory but not inhibitory synapses. Mechanistically, 12-mer-19 interferes with the interaction between neurexin1 and its partners at excitatory synapses, but has little effect on neurexin1's partner at inhibitory synapses. Moreover, 12-mer-NAc didn't have such effects, highlighting the importance of sulfated groups. Our results suggest that extracellular complex glycans may have a selective yet underappreciated role in excitatory synapses, perhaps contributing to the E/I imbalance. Moreover, current studies lay a foundation for future work to dissect the contribution of specific heparan sulfate structures to synaptic morphology and function.","PeriodicalId":12766,"journal":{"name":"Glycobiology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144553372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction to: Ephrin-B1 regulates cell surface residency of heparan sulfate proteoglycans (HSPGs) and complexes with the HSPG CD44V3-10 and fibroblast growth factor receptors. 更正：Ephrin-B1调节硫酸肝素蛋白聚糖（HSPGs）及其与HSPG CD44V3-10和成纤维细胞生长因子受体的复合物的细胞表面驻留。

IF 3.4 3区生物学

Glycobiology Pub Date : 2025-06-23 DOI: 10.1093/glycob/cwaf040

引用次数: 0

The role of gangliosides in male reproduction. 神经节苷在男性生殖中的作用。

IF 3.4 3区生物学

Glycobiology Pub Date : 2025-06-23 DOI: 10.1093/glycob/cwaf036

Kai Wang, Ying Feng, Fang Ma, Jiajie Li, Jing Chen, Xue Ma

{"title":"The role of gangliosides in male reproduction.","authors":"Kai Wang, Ying Feng, Fang Ma, Jiajie Li, Jing Chen, Xue Ma","doi":"10.1093/glycob/cwaf036","DOIUrl":"10.1093/glycob/cwaf036","url":null,"abstract":"Male reproduction is a complex process governed by sophisticated cellular and molecular pathways including sperm production, maturation, and delivery. This review underscores the indispensable role of gangliosides-sialic acid-bearing glycosphingolipids prevalent in the male reproductive system-as key modulators of sperm functionality. Gangliosides, which consist of a ceramide core linked to oligosaccharide chains, are predominantly found on cell plasma membranes, where they play crucial roles in cell signaling, adhesion, recognition, and membrane structure. Extensive research has revealed gangliosides' dynamic contributions to various facets of sperm physiology, such as maturation, capacitation, the acrosome reaction, and ultimately, fertilization. Variability in ganglioside composition and localization during different sperm development stages and within specific areas of the male reproductive tract underscores their importance in sperm functionality and reproductive outcome. Furthermore, disruptions in ganglioside synthesis, transport and distribution on the membrane or surrounding molecules have been associated with male infertility and reproductive dysfunctions, positioning them as potential biomarkers for these conditions. The findings presented in this review not only advance our understanding of the biochemical landscape of male fertility but also propose gangliosides as potential targets for therapeutic intervention, offering a promising avenue for addressing male reproductive disorders. The exploration of gangliosides in the context of male reproduction not only enhances our understanding of male fertility but also paves the way for novel diagnostic and therapeutic strategies in reproductive health. These insights emphasize the urgency and significance of further investigative efforts into ganglioside functions to potentially revolutionize the diagnosis and treatment of male reproductive abnormalities.","PeriodicalId":12766,"journal":{"name":"Glycobiology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144527581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Glyco-Forum.

IF 3.4 3区生物学

Glycobiology Pub Date : 2025-06-23 DOI: 10.1093/glycob/cwaf037

引用次数: 0

Glyco you should know. Glyco你应该知道。

IF 3.4 3区生物学

Glycobiology Pub Date : 2025-06-23 DOI: 10.1093/glycob/cwaf038

Emily Kukan

引用次数: 0

Integrated tumour-immune cell response modelling of luminal a breast cancer details malignant signalling and ST3Gal1 inhibitor-induced reversal. luminal a乳腺癌的综合肿瘤免疫细胞反应模型详细描述了恶性信号传导和ST3Gal1抑制剂诱导的逆转。

IF 3.4 3区生物学

Glycobiology Pub Date : 2025-06-23 DOI: 10.1093/glycob/cwaf035

Hikmet Emre Kaya, Kevin J Naidoo

{"title":"Integrated tumour-immune cell response modelling of luminal a breast cancer details malignant signalling and ST3Gal1 inhibitor-induced reversal.","authors":"Hikmet Emre Kaya, Kevin J Naidoo","doi":"10.1093/glycob/cwaf035","DOIUrl":"10.1093/glycob/cwaf035","url":null,"abstract":"Aberrant O-glycosylation of mucin-type glycopeptide 1 (MUC1) is implicated in cancerous cellular processes involving the manipulation of immune response to favour tumour growth and metastasis. There is an unmet need for systems glycobiology models to probe the relationship between MUC1 O-glycosylation and immune cells within the tumour microenvironment. We expand on the sparsely understood MUC1 and immune cell interactions by building a complete systems model that combines the glycosylation network in the tumour cell with downstream biological networks. An ordinary differential equations-based model of the effect of aberrant glycosylation on immune modulation in breast cancer was constructed. The model comprises three interdependent component models that are MUC1-type O-glycosylation in the tumour cell, chemokine secretion in macrophages, and signal transduction in the tumour cells. A comparative CytoCopasi algorithm was developed to sequentially perturb the networks by an aberrant O-glycosylation. Comparative simulations revealed that upregulation of tumour-associated MUC1 sialyl-T antigen in Luminal A breast cancer stimulated the upregulation of the chemokine CXCL5 in tumour-associated macrophages. Consequently, increased CXCL5 binding by the tumour cell led to a positive feedback loop through overactive signal transduction and autocrine CXCL5 production. Finally, perturbing the glycosylation network with the sialyltransferase inhibitor Soyasaponin-I abrogated the cancerous upregulations in the downstream networks.","PeriodicalId":12766,"journal":{"name":"Glycobiology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12199699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Glyco-Forum.

IF 3.4 3区生物学

Glycobiology Pub Date : 2025-06-02 DOI: 10.1093/glycob/cwaf032

引用次数: 0

In memoriam: Hans Bakker (1963-2025). 纪念：汉斯·巴克（1963-2025）。

IF 3.4 3区生物学

Glycobiology Pub Date : 2025-06-02 DOI: 10.1093/glycob/cwaf034

引用次数: 0

The insight into the biology of five homologous lectins produced by the entomopathogenic bacterium and nematode symbiont Photorhabdus laumondii. 昆虫病原细菌和线虫共生体光habdus laumondii产生的五种同源凝集素的生物学研究。

IF 3.4 3区生物学

Glycobiology Pub Date : 2025-06-02 DOI: 10.1093/glycob/cwaf033

Eva Paulenová, Pavel Dobeš, Filip Melicher, Josef Houser, Lukáš Faltinek, Pavel Hyršl, Michaela Wimmerová

{"title":"The insight into the biology of five homologous lectins produced by the entomopathogenic bacterium and nematode symbiont Photorhabdus laumondii.","authors":"Eva Paulenová, Pavel Dobeš, Filip Melicher, Josef Houser, Lukáš Faltinek, Pavel Hyršl, Michaela Wimmerová","doi":"10.1093/glycob/cwaf033","DOIUrl":"10.1093/glycob/cwaf033","url":null,"abstract":"Photorhabdus laumondii is a well-known bacterium with a complex life cycle involving mutualism with nematodes of the genus Heterorhabditis and pathogenicity towards insect hosts. It provides an excellent model for studying the diverse roles of lectins, saccharide-binding proteins, in both symbiosis and pathogenicity. This study focuses on the seven-bladed β-propeller lectins of P. laumondii (PLLs), examining their biochemical properties (structure and saccharide specificity) and biological functions (gene expression, interactions with the nematode symbiont, and the host immune system response). Structural analyses revealed diverse oligomeric states among PLLs and a unique organisation of binding sites not described outside the PLL lectin family. Lectins exhibited high specificity for fucosylated and O-methylated saccharides with a significant avidity effect for multivalent ligands. Gene expression analysis across bacterial growth phases revealed that PLLs are predominantly expressed during the exponential phase. Interaction studies with the host immune system demonstrated that PLL5 uniquely induced melanisation in Galleria mellonella hemolymph. Furthermore, PLL2, PLL3, and PLL5 interfered with reactive oxygen species production in human blood cells, indicating their potential role in modulating host immune responses. Biofilm formation assays and binding studies with nematode life stages showed no significant involvement of PLLs in nematode colonization. Our findings highlight the primary role of PLLs in Photorhabdus pathogenicity rather than in symbiosis and offer valuable insight into the fascinating dynamics within the Photorhabdus-nematode-insect triparted system.","PeriodicalId":12766,"journal":{"name":"Glycobiology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12203525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144208355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0