Glycobiology最新文献_第9页

The three-sided right-handed β-helix is a versatile fold for glycan interactions. 三面右旋 "绊脚石 "螺旋是一种多用途的糖相互作用折叠结构。

IF 3.4 3区生物学

Glycobiology Pub Date : 2024-05-26 DOI: 10.1093/glycob/cwae037

Audrey A Burnim, Keith Dufault-Thompson, Xiaofang Jiang

{"title":"The three-sided right-handed β-helix is a versatile fold for glycan interactions.","authors":"Audrey A Burnim, Keith Dufault-Thompson, Xiaofang Jiang","doi":"10.1093/glycob/cwae037","DOIUrl":"10.1093/glycob/cwae037","url":null,"abstract":"Interactions between proteins and glycans are critical to various biological processes. With databases of carbohydrate-interacting proteins and increasing amounts of structural data, the three-sided right-handed β-helix (RHBH) has emerged as a significant structural fold for glycan interactions. In this review, we provide an overview of the sequence, mechanistic, and structural features that enable the RHBH to interact with glycans. The RHBH is a prevalent fold that exists in eukaryotes, prokaryotes, and viruses associated with adhesin and carbohydrate-active enzyme (CAZyme) functions. An evolutionary trajectory analysis on structurally characterized RHBH-containing proteins shows that they likely evolved from carbohydrate-binding proteins with their carbohydrate-degrading activities evolving later. By examining three polysaccharide lyase and three glycoside hydrolase structures, we provide a detailed view of the modes of glycan binding in RHBH proteins. The 3-dimensional shape of the RHBH creates an electrostatically and spatially favorable glycan binding surface that allows for extensive hydrogen bonding interactions, leading to favorable and stable glycan binding. The RHBH is observed to be an adaptable domain capable of being modified with loop insertions and charge inversions to accommodate heterogeneous and flexible glycans and diverse reaction mechanisms. Understanding this prevalent protein fold can advance our knowledge of glycan binding in biological systems and help guide the efficient design and utilization of RHBH-containing proteins in glycobiology research.","PeriodicalId":12766,"journal":{"name":"Glycobiology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11129586/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141065216","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. Glyco-Forum.

IF 4.3 3区生物学

Glycobiology Pub Date : 2024-05-26 DOI: 10.1093/glycob/cwae038

引用次数: 0

Novel genetically glycoengineered human dendritic cell model reveals regulatory roles of α2,6-linked sialic acids in DC activation of CD4+ T cells and response to TNFα. 新型基因糖工程人树突状细胞模型揭示了α2,6-连接的硅酸在直流激活 CD4 + T 细胞和对 TNFα 的反应中的调控作用。

IF 3.4 3区生物学

Glycobiology Pub Date : 2024-05-26 DOI: 10.1093/glycob/cwae042

Weihua Tian, Anne Louise Blomberg, Kaylin Elisabeth Steinberg, Betina Lyngfeldt Henriksen, Josefine Søborg Jørgensen, Kerstin Skovgaard, Sarah Line Skovbakke, Steffen Goletz

{"title":"Novel genetically glycoengineered human dendritic cell model reveals regulatory roles of α2,6-linked sialic acids in DC activation of CD4+ T cells and response to TNFα.","authors":"Weihua Tian, Anne Louise Blomberg, Kaylin Elisabeth Steinberg, Betina Lyngfeldt Henriksen, Josefine Søborg Jørgensen, Kerstin Skovgaard, Sarah Line Skovbakke, Steffen Goletz","doi":"10.1093/glycob/cwae042","DOIUrl":"10.1093/glycob/cwae042","url":null,"abstract":"Dendritic cells (DCs) are central for the initiation and regulation of appropriate immune responses. While several studies suggest important regulatory roles of sialoglycans in DC biology, our understanding is still inadequate primarily due to a lack of appropriate models. Previous approaches based on enzymatic- or metabolic-glycoengineering and primary cell isolation from genetically modified mice have limitations related to specificity, stability, and species differences. This study addresses these challenges by introducing a workflow to genetically glycoengineer the human DC precursor cell line MUTZ-3, described to differentiate and maturate into fully functional dendritic cells, using CRISPR-Cas9, thereby providing and validating the first isogenic cell model for investigating glycan alteration on human DC differentiation, maturation, and activity. By knocking out (KO) the ST6GAL1 gene, we generated isogenic cells devoid of ST6GAL1-mediated α(2,6)-linked sialylation, allowing for a comprehensive investigation into its impact on DC function. Glycan profiling using lectin binding assay and functional studies revealed that ST6GAL1 KO increased the expression of important antigen presenting and co-stimulatory surface receptors and a specifically increased activation of allogenic human CD4 + T cells. Additionally, ST6GAL1 KO induces significant changes in surface marker expression and cytokine response to TNFα-induced maturation, and it affects migration and the endocytic capacity. These results indicate that genetic glycoengineering of the isogenic MUTZ-3 cellular model offers a valuable tool to study how specific glycan structures influence human DC biology, contributing to our understanding of glycoimmunology.","PeriodicalId":12766,"journal":{"name":"Glycobiology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141316939","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

Glucosylceramides impact cellulose deposition and cellulose synthase complex motility in Arabidopsis. 葡萄糖甘油三酯影响拟南芥中纤维素的沉积和纤维素合成酶复合体的运动。

IF 3.4 3区生物学

Glycobiology Pub Date : 2024-04-24 DOI: 10.1093/glycob/cwae035

Jose A Villalobos, Rebecca E Cahoon, Edgar B Cahoon, Ian S Wallace

{"title":"Glucosylceramides impact cellulose deposition and cellulose synthase complex motility in Arabidopsis.","authors":"Jose A Villalobos, Rebecca E Cahoon, Edgar B Cahoon, Ian S Wallace","doi":"10.1093/glycob/cwae035","DOIUrl":"10.1093/glycob/cwae035","url":null,"abstract":"Cellulose is an abundant component of plant cell wall matrices, and this para-crystalline polysaccharide is synthesized at the plasma membrane by motile Cellulose Synthase Complexes (CSCs). However, the factors that control CSC activity and motility are not fully resolved. In a targeted chemical screen, we identified the alkylated nojirimycin analog N-Dodecyl Deoxynojirimycin (ND-DNJ) as a small molecule that severely impacts Arabidopsis seedling growth. Previous work suggests that ND-DNJ-related compounds inhibit the biosynthesis of glucosylceramides (GlcCers), a class of glycosphingolipid associated with plant membranes. Our work uncovered major changes in the sphingolipidome of plants treated with ND-DNJ, including reductions in GlcCer abundance and altered acyl chain length distributions. Crystalline cellulose content was also reduced in ND-DNJ-treated plants as well as plants treated with the known GlcCer biosynthesis inhibitor N-[2-hydroxy-1-(4-morpholinylmethyl)-2-phenyl ethyl]-decanamide (PDMP) or plants containing a genetic disruption in GLUCOSYLCERAMIDE SYNTHASE (GCS), the enzyme responsible for sphingolipid glucosylation that results in GlcCer synthesis. Live-cell imaging revealed that CSC speed distributions were reduced upon treatment with ND-DNJ or PDMP, further suggesting an important relationship between glycosylated sphingolipid composition and CSC motility across the plasma membrane. These results indicate that multiple interventions compromising GlcCer biosynthesis disrupt cellulose deposition and CSC motility, suggesting that GlcCers regulate cellulose biosynthesis in plants.","PeriodicalId":12766,"journal":{"name":"Glycobiology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140864441","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

Inhibitors of dermatan sulfate epimerase 1 decreased accumulation of glycosaminoglycans in mucopolysaccharidosis type I fibroblasts. 硫酸皮质酯表聚酶1抑制剂可减少粘多糖病I型成纤维细胞中糖胺聚糖的积累。

IF 3.4 3区生物学

Glycobiology Pub Date : 2024-04-24 DOI: 10.1093/glycob/cwae025

Marco Maccarana, Binjie Li, Honglian Li, Jianping Fang, Mingjia Yu, Jin-Ping Li

{"title":"Inhibitors of dermatan sulfate epimerase 1 decreased accumulation of glycosaminoglycans in mucopolysaccharidosis type I fibroblasts.","authors":"Marco Maccarana, Binjie Li, Honglian Li, Jianping Fang, Mingjia Yu, Jin-Ping Li","doi":"10.1093/glycob/cwae025","DOIUrl":"10.1093/glycob/cwae025","url":null,"abstract":"Genetic deficiency of alpha-L-iduronidase causes mucopolysaccharidosis type I (MPS-I) disease, due to accumulation of glycosaminoglycans (GAGs) including chondroitin/dermatan sulfate (CS/DS) and heparan sulfate (HS) in cells. Currently, patients are treated by infusion of recombinant iduronidase or by hematopoietic stem cell transplantation. An alternative approach is to reduce the L-iduronidase substrate, through limiting the biosynthesis of iduronic acid. Our earlier study demonstrated that ebselen attenuated GAGs accumulation in MPS-I cells, through inhibiting iduronic acid producing enzymes. However, ebselen has multiple pharmacological effects, which prevents its application for MPS-I. Thus, we continued the study by looking for novel inhibitors of dermatan sulfate epimerase 1 (DS-epi1), the main responsible enzyme for production of iduronic acid in CS/DS chains. Based on virtual screening of chemicals towards chondroitinase AC, we constructed a library with 1,064 compounds that were tested for DS-epi1 inhibition. Seventeen compounds were identified to be able to inhibit 27%-86% of DS-epi1 activity at 10 μM. Two compounds were selected for further investigation based on the structure properties. The results show that both inhibitors had a comparable level in inhibition of DS-epi1while they had negligible effect on HS epimerase. The two inhibitors were able to reduce iduronic acid biosynthesis in CS/DS and GAG accumulation in WT and MPS-I fibroblasts. Docking of the inhibitors into DS-epi1 structure shows high affinity binding of both compounds to the active site. The collected data indicate that these hit compounds may be further elaborated to a potential lead drug used for attenuation of GAGs accumulation in MPS-I patients.","PeriodicalId":12766,"journal":{"name":"Glycobiology","volume":"34 6","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11101759/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140957242","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

Relevance of glyco-biomakers and glycan profiles in cancer stem cells. 癌症干细胞中的糖生物制造者和糖概况的相关性。

IF 3.4 3区生物学

Glycobiology Pub Date : 2024-04-24 DOI: 10.1093/glycob/cwad019

Rohit Pujari, Shiv Kumar Dubey

{"title":"Relevance of glyco-biomakers and glycan profiles in cancer stem cells.","authors":"Rohit Pujari, Shiv Kumar Dubey","doi":"10.1093/glycob/cwad019","DOIUrl":"10.1093/glycob/cwad019","url":null,"abstract":"Altered and aberrant glycosylation signatures have been linked to being a hallmark in a variety of human disorders including cancer. Cancer stem cells (CSCs), capable of self-renewal and differentiation, have recently been credited with a unique notion of disease genesis and implicated as the cause for initiation and recurrence of the disease in a new regime of neoplastic transformations hypothesis. Many biomarkers relating to diagnostic and prognostic intents have been discovered using the ubiquitous and abundant surface glycan patterns on CSCs. Various technological advancements have been developed to identify and determine concerns with glycosylation structure. However, the nature and purpose of the glycan moiety on these glycosylation pattern have not yet been thoroughly investigated. This review, thus, summarizes the process of glycosylation in CSCs, variations in glycosylation patterns in various stem cells, aberrant glycosylation patterns in cancer, the role of glycosylation in tumor cell adhesion, cell-matrix interactions, and signaling, as well as cancer detection and treatment. The function of carbohydrates as prospective serum biomarkers, some clinically authorized biomarkers, and potential novel biomarkers relating to cancer disease diagnosis and prognosis are also discussed in the review.","PeriodicalId":12766,"journal":{"name":"Glycobiology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10821325","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. Glyco-Forum.

IF 4.3 3区生物学

Glycobiology Pub Date : 2024-04-24 DOI: 10.1093/glycob/cwae034

引用次数: 0

Glyco-Forum. Glyco-Forum.

IF 4.3 3区生物学

Glycobiology Pub Date : 2024-04-24 DOI: 10.1093/glycob/cwae034

引用次数: 0

Variability of human Alpha-1-acid glycoprotein N-glycome in a Caucasian population. 高加索人群中人类α-1-酸糖蛋白 N-糖蛋白的变异性。

IF 3.4 3区生物学

Glycobiology Pub Date : 2024-04-24 DOI: 10.1093/glycob/cwae031

Frano Vučković, Mislav Novokmet, Dinko Šoić, Jerko Štambuk, Ivana Kolčić, Ozren Polašek, Gordan Lauc, Olga Gornik, Toma Keser

{"title":"Variability of human Alpha-1-acid glycoprotein N-glycome in a Caucasian population.","authors":"Frano Vučković, Mislav Novokmet, Dinko Šoić, Jerko Štambuk, Ivana Kolčić, Ozren Polašek, Gordan Lauc, Olga Gornik, Toma Keser","doi":"10.1093/glycob/cwae031","DOIUrl":"10.1093/glycob/cwae031","url":null,"abstract":"Aim: Alpha-1-acid glycoprotein (AGP) is a highly glycosylated protein in human plasma and one of the most abundant acute phase proteins in humans. Glycosylation plays a crucial role in its biological functions, and alterations in AGP N-glycome have been associated with various diseases and inflammatory conditions. However, large-scale studies of AGP N-glycosylation in the general population are lacking.Methods: Using recently developed high-throughput glycoproteomic workflow for site-specific AGP N-glycosylation analysis, 803 individuals from the Croatian island of Korcula were analyzed and their AGP N-glycome data associated with biochemical and physiological traits, as well as different environmental factors.Results: After regression analysis, we found that AGP N-glycosylation is strongly associated with sex, somewhat less with age, along with multiple biochemical and physiological traits (e.g. BMI, triglycerides, uric acid, glucose, smoking status, fibrinogen).Conclusion: For the first time we have extensively explored the inter-individual variability of AGP N-glycome in a general human population, demonstrating its changes with sex, age, biochemical, and physiological status of individuals, providing the baseline for future population and clinical studies.","PeriodicalId":12766,"journal":{"name":"Glycobiology","volume":"34 6","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140862718","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 You Should Know. 你应该知道的 Glyco

IF 4.3 3区生物学

Glycobiology Pub Date : 2024-04-19 DOI: 10.1093/glycob/cwae022

Emily Kukan

引用次数: 0