Glycobiology最新文献

{"title":"Ten years of integrative carbohydrate structure validation with Privateer.","authors":"Lucy C Schofield, Jordan S Dialpuri, Haroldas Bagdonas, Lou Holland, Phuong Thao Pham, Shuai Wang, William Cook, Jon Agirre","doi":"10.1093/glycob/cwag068","DOIUrl":"10.1093/glycob/cwag068","url":null,"abstract":"<p><p>Understanding glycoprotein structures is critical for understanding their biological roles, yet despite the moderate size of the glycans, determining the structure of these atomic models presents unique challenges. Originally designed to help mine the Protein Data Bank for monosaccharides and their context, the Privateer carbohydrate validation software has evolved to become ubiquitous in carbohydrate model building workflows. Privateer detects issues affecting sugar stereochemistry, regiochemistry, pyranoside and furanoside ring conformation, as well as overall glycan conformation and composition. Supporting both X-ray crystallography and cryo-electron microscopy data, Privateer can communicate with refinement software to help restrain sugar rings to their minimal-energy conformations. In this work, we reflect on a decade of Privateer, documenting its core processes and best practices to serve as the primary citation for the software.</p>","PeriodicalId":12766,"journal":{"name":"Glycobiology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148792220","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}

{"title":"Protein O-Mannosyltransferases in development and disease: evolutionary and functional insights from model organisms.","authors":"Caden Summers, Saniya Dauletbayeva, Boris Novikov, Isabelle Nguyen, M Chiara Manzini, Vladislav Panin","doi":"10.1093/glycob/cwag071","DOIUrl":"10.1093/glycob/cwag071","url":null,"abstract":"<p><p>Protein O-mannosylation is an evolutionarily conserved post-translational modification essential for neuromuscular development and physiology. The obligate heteromeric complex of protein O-mannosyltransferase 1 and 2 (POMT1/2) initiates O-mannosylation of α-dystroglycan and a limited number of known additional substrates in the endoplasmic reticulum. In humans, defects in these enzymes disrupt dystroglycan function, leading to impaired extracellular matrix interactions that contribute to a spectrum of severe congenital muscular dystrophies termed dystroglycanopathies. However, mounting evidence indicates that POMTs have additional functional substrates that substantially contribute to POMT1/2 mutant phenotypes through dystroglycan-independent mechanisms. This review examines POMT1/2 function through a comparative evolutionary lens using model organisms, such as Drosophila and zebrafish and discusses O-mannosylation substrates beyond dystroglycan. We review the functions of POMT1/2 in muscle and the nervous system in Drosophila, including the interplay with receptor protein tyrosine phosphatases, a novel conserved family of substrates with essential functions in neural circuit formation. In the zebrafish model, POMT1/2 mutant phenotypes recapitulate multi-tissue defects associated with dystroglycanopathies, revealing compensatory mechanisms with broad implications for understanding these diseases while also suggesting the involvement of dystroglycan-independent pathomechanisms. Together, these animal models provide a tiered experimental framework, combining the advantages of simplified glycan architectures, powerful genetic tools, and comprehensively characterized development, with evolutionary conservation of core molecular players involved in human disease. These and other animal models will continue to make invaluable contributions towards dissecting POMT1/2 function at the molecular, cellular, and genetic levels, leading to a better understanding of the pathological mechanisms of dystroglycanopathies.</p>","PeriodicalId":12766,"journal":{"name":"Glycobiology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148864762","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}

{"title":"Programmable HMO biosynthesis enabled by human cell-based glycoengineering.","authors":"Stijn Kruf, Roy J B M Delahaije, Morihisa Fujita, Christian Büll","doi":"10.1093/glycob/cwag066","DOIUrl":"10.1093/glycob/cwag066","url":null,"abstract":"<p><p>The lactating mammary gland is uniquely adapted to synthesize unconjugated free glycans known as human milk oligosaccharides (HMOs). HMO biosynthesis is initiated by the formation of lactose, the common precursor from which structurally diverse neutral and acidic oligosaccharides are generated through the sequential action of Golgi-resident glycosyltransferases. Although microbial fermentation and chemical synthesis have enabled production of selected HMOs, human cell-based platforms remain largely unexplored despite providing the native glycosylation machinery required for HMO assembly. Consequently, the contributions of individual glycosyltransferases to HMO biosynthesis have remained difficult to define. Here, we describe the construction of HMO biosynthesis in human embryonic kidney (HEK293) cells through constitution of the lactose synthase complex and systematic engineering of downstream glycosyltransferases. This modular approach enables programmable production of structurally defined HMOs, including both simple sialylated oligosaccharides and more complex type-I and type-II structures, while providing a tractable platform for assigning glycosyltransferase functions within the HMO biosynthetic pathway. Together, this establishes mammalian glycoengineering as a versatile system for investigating HMO biosynthesis and for the tailored production of biologically relevant HMOs.</p>","PeriodicalId":12766,"journal":{"name":"Glycobiology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13622347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148792173","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}

{"title":"Glyco you should know.","authors":"Katherine Wongtrakul-Kish","doi":"10.1093/glycob/cwag089","DOIUrl":"10.1093/glycob/cwag089","url":null,"abstract":"","PeriodicalId":12766,"journal":{"name":"Glycobiology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180923","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}

{"title":"Glyco-Forum.","authors":"","doi":"10.1093/glycob/cwag091","DOIUrl":"https://doi.org/10.1093/glycob/cwag091","url":null,"abstract":"","PeriodicalId":12766,"journal":{"name":"Glycobiology","volume":"36 11","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149192961","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}

{"title":"Recent immunoglobulin G1 engineering strategies to modulate immune effector functions for therapeutics.","authors":"Alexander R Davis, Adam W Barb","doi":"10.1093/glycob/cwag098","DOIUrl":"10.1093/glycob/cwag098","url":null,"abstract":"<p><p>IgG is the most common scaffold used for antibody-based therapeutics. Utilization of the ever-expanding knowledge base of the IgG scaffold provides a wealth of design options for therapeutic development. These therapeutics apply varied engineering strategies in various combinations utilizing three key IgG features: the crystallizable fragment (Fc), antigen-binding fragment (Fab), and the conserved N-glycans. Designs may be as simple as amino acid variants to modulate effector function or as complex as large designs incorporating additional Fab, Fc, and non-IgG domain fusions to modulate effector molecule recognition, valency, and antigen specificity. The engineering strategies and basic knowledge supporting these developments have been the subject of rapid expansion. Here we review multiple approaches and advances with a focus on the last five years.</p>","PeriodicalId":12766,"journal":{"name":"Glycobiology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149181076","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}

{"title":"O-GlcNAcylation in Macrophage Functions.","authors":"José Luis Sánchez-Salgado, Alí Pereyra, Wilton Henao, Johana Torres-Barrón, Gustavo Ortiz-Chavez, Eleazar Ramírez, Edgar Zenteno Galindo","doi":"10.1093/glycob/cwag084","DOIUrl":"https://doi.org/10.1093/glycob/cwag084","url":null,"abstract":"<p><p>Macrophages are central effectors of the immune system. These cells exhibit a wide range of functions, including inflammation, phagocytosis, antigen presentation, cytokine secretion, and tissue repair, all of which are tightly coupled to their metabolic state. O-GlcNAcylation, a reversible post-translational modification catalyzed exclusively by OGT and OGA, integrates glucose flux through the hexosamine biosynthetic pathway with the regulation of key immune mechanisms. This review evaluates the effect of O-GlcNAcylation on the expression and localization of pattern recognition receptors, endosome maturation, phagocytic capacity, reactive oxygen species production, and pro- and anti-inflammatory polarization.</p>","PeriodicalId":12766,"journal":{"name":"Glycobiology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149038201","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}

{"title":"Targeted Control of Protein O-GlcNAcylation in Living Cells.","authors":"Tongyang Xu, Billy Wai-Lung Ng","doi":"10.1093/glycob/cwag081","DOIUrl":"https://doi.org/10.1093/glycob/cwag081","url":null,"abstract":"<p><p>O-linked N-acetylglucosamine glycosylation (O-GlcNAcylation) regulates many intracellular proteins, but linking a cellular phenotype to O-GlcNAcylation of a specific substrate remains difficult. Global perturbation of O-GlcNAc transferase (OGT) or O-GlcNAcase (OGA) changes many proteins at once and therefore provides limited information about individual substrates. Protein-selective approaches address this problem by directing OGT or OGA activity toward chosen proteins in living cells. Here, we review small-molecule recruiters, nanobody-based systems, inducible recruitment strategies, RNA aptamers, and complementary site-level approaches. We compare what each method can establish and the controls needed for interpretation, with particular attention to target engagement, target-protein O-GlcNAcylation, site assignment, selectivity, and functional validation. Together, these approaches provide increasingly direct ways to define how O-GlcNAcylation of individual proteins contributes to cellular function.</p>","PeriodicalId":12766,"journal":{"name":"Glycobiology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149038238","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}

{"title":"Conformational exceptions in glycoside hydrolase reactivity.","authors":"Santiago Alonso-Gil","doi":"10.1093/glycob/cwag082","DOIUrl":"https://doi.org/10.1093/glycob/cwag082","url":null,"abstract":"<p><p>Glycoside hydrolases (GHs) accelerate glycosidic bond cleavage by coupling active-site architecture, the geometry required for substitution at the anomeric center, and the conformational landscape of the -1 sugar. This coupling is often summarized as family-dependent conformational itineraries that connect Michaelis complexes to oxocarbenium-ion-like transition states (and, for retaining enzymes, to covalent intermediates). However, crystallographic snapshots sometimes reveal complexes in which the -1 sugar remains close to a ground-state-like 4C₁ chair or adopts noncanonical puckers such as E₅. In this Review, we reassess such observations within a cautious physical-organic framework. Here, \"exception\" is used in a mechanistic rather than statistical sense: the aim is to document and interpret departures from the conformational behaviour expected from accepted stereochemistry itinerary relationships, not to estimate the relative abundance of such cases in the Protein Data Bank. Chair-like 4C₁ complexes should not be interpreted as evidence for a new transition-state geometry; rather, they may represent recognition or pre-reactive minima in which catalytic residues are positioned near C1 but additional late, transient, or ensemble distortion is still required to reach an in-line, oxocarbenium-ion-like transition state. We further discuss how metal coordination and active-site constraints in α-mannosidases can stabilize alternative pre-reactive basins-exemplified by E₅ complexes in GH38 and GH92-while preserving access to transition-state-competent regions. Finally, we outline how structural descriptors, on-enzyme dynamics, and intrinsic quantum-mechanical \"preactivation\" indices can help distinguish genuinely productive noncanonical states from crystallographic ground-state snapshots.</p>","PeriodicalId":12766,"journal":{"name":"Glycobiology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149038228","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}

{"title":"Temporal N-glycoproteomic differences between COVID-19 survivors and non-survivors at hospital admission and beyond.","authors":"Xue Yu, Kelly Dingess, Rita Pavasini, Gianluca Campo, Spadaro Savino, Albert J R Heck, Karli R Reiding","doi":"10.1093/glycob/cwag079","DOIUrl":"https://doi.org/10.1093/glycob/cwag079","url":null,"abstract":"<p><p>COVID-19 has proven to have a wide range of symptoms in human patients, prompting investigation into relevant biomarkers and underlying biological mechanisms. In this study, we aimed to develop a robust quantitative N-glycoproteomics approach for complex plasma samples and to characterize the altered glycosylation profiles associated with COVID-19 severity. We analyzed plasma samples from 16 survivors and 15 non-survivors, collected at three distinct time points following hospital admission. Using data-dependent acquisition (DDA) mass spectrometry, combined with a spectral library and the \"match-between-runs\" strategy, we profiled 397 unique glycopeptides and 62 glycan species, derived from 50 proteins across 86 glycosylation sites. By assessing both cross-sectional differences and longitudinal changes, we identified several site-specific glycosylation alterations that may serve as potential markers of disease severity. The most notable site-specific change was in the complement C1q A-chain (C1QA) at Asn146, with non-survivors having less fucosylation at hospital admission. We also observed increased bisection of immunoglobulins in non-survivors (IgG3/4 Asn177 and IgM Asn146) and glycosylation pattern changes in acute-phase proteins. Longitudinally, the fucosylation levels of C1QA increased in the non-survivors, whereas they decreased in the survivors. These findings highlight the potential value of site-specific glycoproteomic profiling for improving the molecular understanding of COVID-19 severity.</p>","PeriodicalId":12766,"journal":{"name":"Glycobiology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149024834","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}