Glycobiology最新文献

{"title":"Why nature evolved GPI-anchored proteins: unique structure characteristics enable versatile cell surface functions.","authors":"Qi Zhang, Morihisa Fujita","doi":"10.1093/glycob/cwae089","DOIUrl":"10.1093/glycob/cwae089","url":null,"abstract":"<p><p>It remains a mystery why nature evolved the unique structural characteristics of GPI-anchored proteins (GPI-APs) and continues to sustain the complex, energy-intensive process of synthesizing these proteins. GPI-APs, despite their small size, rely on the coordinated activity of nearly 30 genes for their synthesis and remodeling, raising important evolutionary questions. The biological advantages of GPI-APs lie in their ability to rapidly redistribute across the cell membrane, localize within lipid rafts, utilize unique intracellular trafficking pathways, and function as both membrane-bound and soluble proteins. These properties allow GPI-APs to participate in diverse cellular processes such as synaptic plasticity, immune regulation, and signal transduction, highlighting their indispensable roles. Additionally, the shedding capability of GPI-APs extends their functional reach, adding further versatility to their biological roles. This review not only summarizes these key insights but also explores the broader implications of GPI-APs in cell signaling and disease. By understanding the evolutionary necessity of GPI-APs, we can better appreciate their complexity and potential as therapeutic targets.</p>","PeriodicalId":12766,"journal":{"name":"Glycobiology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11632373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142618730","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":"Interactions that define the arrangement of sugar-binding sites in BDCA-2 and dectin-2 dimers.","authors":"Yu Liu, Jong-Won Kim, Hadar Feinberg, Nikeel Cull, William I Weis, Maureen E Taylor, Kurt Drickamer","doi":"10.1093/glycob/cwae082","DOIUrl":"10.1093/glycob/cwae082","url":null,"abstract":"<p><p>The sugar-binding receptors dectin-2 and blood dendritic cell antigen 2 (BDCA-2) bind oligosaccharide ligands through extracellular carbohydrate-recognition domains (CRDs) and initiate intracellular signaling through Fc receptor γ adapters (FcRγ). Dectin-2 stimulates macrophages in response to pathogen binding while BDCA-2 modulates cytokine production in plasmacytoid dendritic cells. The oligomeric states of these receptors and the orientations of their CRDs have been investigated by analysis of a naturally occurring disulfide-bonded variant of BDCA-2 and by replacement of transmembrane domains with N-terminal dimerization domains to create extracellular domain dimers of both dectin-2 and BDCA-2. Analysis of these constructs, as well as previously described crystal structures of the CRDs from these proteins and a novel structure of an extended version of the extracellular domain of dectin-2, showed that there is only limited interaction of the CRDs in the dimers, but interactions can be stabilized by the presence of the neck region. The resulting orientation of sugar-binding sites in the dimers would favor crosslinking of multiple dimers by oligosaccharide ligands, causing clustering of FcRγ to initiate signaling.</p>","PeriodicalId":12766,"journal":{"name":"Glycobiology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11632364/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371622","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":"Society for Glycobiology awards-2024.","authors":"","doi":"10.1093/glycob/cwae077","DOIUrl":"https://doi.org/10.1093/glycob/cwae077","url":null,"abstract":"","PeriodicalId":12766,"journal":{"name":"Glycobiology","volume":"34 11","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142389845","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":"α-Mannosylated HLA-II glycopeptide antigens dominate the immunopeptidome of immortalised cells and tumour tissues.","authors":"Hayley Goodson, Rebeca Kawahara, Joshua Fehring, Anthony W Purcell, Nathan P Croft, Morten Thaysen-Andersen","doi":"10.1093/glycob/cwae057","DOIUrl":"10.1093/glycob/cwae057","url":null,"abstract":"<p><p>Immunopeptides are cell surface-located protein fragments that aid our immune system to recognise and respond to pathogenic insult and malignant transformation. In this two-part communication, we firstly summarise and reflect on our recent discovery documenting that MHC-II-bound immunopeptides from immortalised cell lines prevalently carry N-glycans that differ from the cellular glycoproteome (Goodson, Front Immunol, 2023). These findings are important as immunopeptide glycosylation remains poorly understood in immunosurveillance. The study also opened up new technical and biological questions that we address in the second part of this communication. Our study highlighted that the performance of the search engines used to detect glycosylated immunopeptides from LC-MS/MS data remains untested and, importantly, that little biochemical in vivo evidence is available to document the nature of glycopeptide antigens in tumour tissues. To this end, we compared the N-glycosylated MHC-II-bound immunopeptides that were reported from tumour tissues of 14 meningioma patients in the MSFragger-HLA-Glyco database (Bedran, Nat Commun, 2023) to those we identified with the commercial Byonic software. Encouragingly, the search engines produced similar outputs supporting that N-glycosylated MHC-II-bound immunopeptides are prevalent in meningioma tumour tissues. Consistent also with in vitro findings, the tissue-derived MHC-II-bound immunopeptides were found to predominantly carry hyper-processed (paucimannosidic- and chitobiose core-type) and hypo-processed (oligomannosidic-type) N-glycans that varied in prevalence and distribution between patients. Taken together, evidence is emerging suggesting that α-mannosidic glycoepitopes abundantly decorate MHC-II-bound immunopeptides presented in both immortalised cells and tumour tissues warranting further research into their functional roles in immunosurveillance.</p>","PeriodicalId":12766,"journal":{"name":"Glycobiology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11441994/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141874641","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":"Development of new NGLY1 assay systems - toward developing an early screening method for NGLY1 deficiency.","authors":"Hiroto Hirayama, Haruhiko Fujihira, Tadashi Suzuki","doi":"10.1093/glycob/cwae067","DOIUrl":"10.1093/glycob/cwae067","url":null,"abstract":"<p><p>Cytosolic peptide: N-glycanase (PNGase/NGLY1 in mammals) is an amidase (EC:3.5.1.52) widely conserved in eukaryotes. It catalyzes the removal of N-glycans on glycoproteins, converting N-glycosylated Asn into Asp residues. This enzyme also plays a role in the quality control system for nascent glycoproteins. Since the identification of a patient with an autosomal recessive genetic disorder caused by NGLY1 gene dysfunction, known as NGLY1 deficiency or NGLY1 congenital disorder of deglycosylation (OMIM: 615273), in 2012, more than 100 cases have been reported worldwide. NGLY1 deficiency is characterized by a wide array of symptoms, such as global mental delay, intellectual disability, abnormal electroencephalography findings, seizure, movement disorder, hypolacrima or alacrima, and liver dysfunction. Unfortunately, no effective therapeutic treatments for this disease have been established. However, administration of adeno-associated virus 9 (AAV9) vector harboring human NGLY1 gene to an NGLY1-deficient rat model (Ngly1-/- rat) by intracerebroventricular injection was found to drastically improve motor function defects. This observation indicated that early therapeutic intervention could alleviate various symptoms originating from central nervous system dysfunction in this disease. Therefore, there is a keen interest in the development of facile diagnostic methods for NGLY1 deficiency. This review summarizes the history of assay development for PNGase/NGLY1 activity, as well as the recent progress in the development of novel plate-based assay systems for NGLY1, and also discusses future perspectives.</p>","PeriodicalId":12766,"journal":{"name":"Glycobiology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11442003/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142106694","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":"The Human Glycome Atlas project for cataloging all glycan-related omics data in human.","authors":"Kiyoko F Aoki-Kinoshita, Yukie Akune-Taylor, Hiromune Ando, Kiyohiko Angata, Morihisa Fujita, Jun-Ichi Furukawa, Hiroyuki Kaji, Koichi Kato, Ken Kitajima, Yasuhiko Kizuka, Yusuke Matsui, Kazuki Nakajima, Shoko Nishihara, Tetsuya Okajima, Kazuma Sakamoto, Chihiro Sato, Morten Thaysen-Andersen, Akira Togayachi, Hirokazu Yagi, Achille Zappa, Kenji Kadomatsu","doi":"10.1093/glycob/cwae052","DOIUrl":"10.1093/glycob/cwae052","url":null,"abstract":"<p><p>The Human Glycome Atlas (HGA) Project was launched in April 2023, spearheaded by three Japanese institutes: the Tokai National Higher Education and Research System, the National Institutes of Natural Sciences, and Soka University. This was the first time that a field in the life sciences was adopted by the Ministry of Education, Culture, Sports, Science and Technology (MEXT) for a Large-scale Academic Frontiers Promotion Project. This project aims to construct a knowledgebase of human glycans and glycoproteins as a standard for the human glycome. A high-throughput pipeline for comprehensively analyzing 20,000 blood samples in its first five years is planned, at which time an access-controlled version of a human glycomics knowledgebase, called TOHSA, will be released. By the end of the final tenth year, TOHSA will provide a central resource linking human glycan data with other omics data including disease-related information.</p>","PeriodicalId":12766,"journal":{"name":"Glycobiology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11729707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141765880","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":"N-glycoproteomic and proteomic alterations in SRD5A3-deficient fibroblasts.","authors":"Kishore Garapati, Wasantha Ranatunga, Neha Joshi, Rohit Budhraja, Saniha Sabu, Kristin A Kantautas, Graeme Preston, Ethan O Perlstein, Tamas Kozicz, Eva Morava, Akhilesh Pandey","doi":"10.1093/glycob/cwae076","DOIUrl":"10.1093/glycob/cwae076","url":null,"abstract":"<p><p>SRD5A3-CDG is a congenital disorder of glycosylation (CDG) resulting from pathogenic variants in SRD5A3 and follows an autosomal recessive inheritance pattern. The enzyme encoded by SRD5A3, polyprenal reductase, plays a crucial role in synthesizing lipid precursors essential for N-linked glycosylation. Despite insights from functional studies into its enzymatic function, there remains a gap in understanding global changes in patient cells. We sought to identify N-glycoproteomic and proteomic signatures specific to SRD5A3-CDG, potentially aiding in biomarker discovery and advancing our understanding of disease mechanisms. Using tandem mass tag (TMT)-based relative quantitation, we analyzed fibroblasts derived from five patients along with control fibroblasts. N-glycoproteomics analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS) identified 3,047 glycopeptides with 544 unique N-glycosylation sites from 276 glycoproteins. Of these, 418 glycopeptides showed statistically significant changes with 379 glycopeptides decreased (P < 0.05) in SRD5A3-CDG patient-derived samples. These included high mannose, complex and hybrid glycan-bearing glycopeptides. High mannose glycopeptides from protocadherin Fat 4 and integrin alpha-11 and complex glycopeptides from CD55 were among the most significantly decreased glycopeptides. Proteomics analysis led to the identification of 5,933 proteins, of which 873 proteins showed statistically significant changes. Decreased proteins included cell surface glycoproteins, various mitochondrial protein populations and proteins involved in the N-glycosylation pathway. Lysosomal proteins such as N-acetylglucosamine-6-sulfatase and procathepsin-L also showed reduced levels of phosphorylated mannose-containing glycopeptides. Our findings point to disruptions in glycosylation pathways as well as energy metabolism and lysosomal functions in SRD5A3-CDG, providing clues to improved understanding and management of patients with this disorder.</p>","PeriodicalId":12766,"journal":{"name":"Glycobiology","volume":"34 11","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7617596/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365051","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":"Glycoconjugate vaccines: platforms and adjuvants for directed immunity.","authors":"Valerie Lensch, Jeremiah A Johnson, Laura L Kiessling","doi":"10.1093/glycob/cwae092","DOIUrl":"10.1093/glycob/cwae092","url":null,"abstract":"<p><p>Central to immune recognition is the glycocalyx, a glycan-rich coat on all cells that plays a crucial role in interactions that enable pathogen detection and activation of immune defenses. Pathogens and cancerous cells often display distinct glycans on their surfaces, making these saccharide antigens prime targets for vaccine development. However, carbohydrates alone generally serve as poor immunogens due to their often weak binding affinities, inability to effectively recruit T cell help, and reliance on adjuvants to iboost immune activation. The introduction of glycoconjugate vaccines, initially involving the covalent coupling of carbohydrate antigens to carrier proteins, marked a pivotal advancement by facilitating neutralizing antibody production against carbohydrate targets. Despite successes in generating glycoconjugate vaccines against certain bacterial diseases, challenges persist in creating effective vaccines against numerous intracellular pathogens and non-communicable diseases such as cancer. In this review, we highlight new developments in conjugate vaccine platforms aim to overcome these limitations by optimizing the display of glycan and T cell epitopes as well as incorporating defined carbohydrate adjuvants to direct tailored immune responses. These advancements promise to improve the effectiveness of carbohydrate-based vaccines and broaden their coverage against a wide range of diseases.</p>","PeriodicalId":12766,"journal":{"name":"Glycobiology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11604072/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142727775","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":"Lilyanna C Massman","doi":"10.1093/glycob/cwae073","DOIUrl":"https://doi.org/10.1093/glycob/cwae073","url":null,"abstract":"","PeriodicalId":12766,"journal":{"name":"Glycobiology","volume":"34 11","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365050","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":"GlycoForum.","authors":"Karen Colley","doi":"10.1093/glycob/cwae079","DOIUrl":"https://doi.org/10.1093/glycob/cwae079","url":null,"abstract":"","PeriodicalId":12766,"journal":{"name":"Glycobiology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142345093","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}