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Glycomics is the comprehensive study of glycomes, including genetic, physiologic, pathologic, and other aspects. Glycomics "is the systematic study of all glycan structures of a given cell type or organism" and is a subset of glycobiology. The term glycomics is derived from the chemical prefix for sweetness or a sugar, "glyco-", and was formed to follow the omics naming convention established by genomics and proteomics.
A microarray is a multiplex lab-on-a-chip. Its purpose is to simultaneously detect the expression of thousands of biological interactions. It is a two-dimensional array on a solid substrate—usually a glass slide or silicon thin-film cell—that assays (tests) large amounts of biological material using high-throughput screening miniaturized, multiplexed and parallel processing and detection methods. The concept and methodology of microarrays was first introduced and illustrated in antibody microarrays by Tse Wen Chang in 1983 in a scientific publication and a series of patents. The "gene chip" industry started to grow significantly after the 1995 Science Magazine article by the Ron Davis and Pat Brown labs at Stanford University. With the establishment of companies, such as Affymetrix, Agilent, Applied Microarrays, Arrayjet, Illumina, and others, the technology of DNA microarrays has become the most sophisticated and the most widely used, while the use of protein, peptide and carbohydrate microarrays is expanding.
A glycome is the entire complement or complete set of all sugars, whether free or chemically bound in more complex molecules, of an organism. An alternative definition is the entirety of carbohydrates in a cell. The glycome may in fact be one of the most complex entities in nature. "Glycomics, analogous to genomics and proteomics, is the systematic study of all glycan structures of a given cell type or organism" and is a subset of glycobiology.
The Consortium for Functional Glycomics (CFG) is a large research initiative funded in 2001 by a glue grant from the National Institute of General Medical Sciences (NIGMS) to “define paradigms by which protein-carbohydrate interactions mediate cell communication”. To achieve this goal, the CFG studies the functions of:
Defined in the narrowest sense, glycobiology is the study of the structure, biosynthesis, and biology of saccharides that are widely distributed in nature. Sugars or saccharides are essential components of all living things and aspects of the various roles they play in biology are researched in various medical, biochemical and biotechnological fields.
Lectins are carbohydrate-binding proteins that are highly specific for sugar groups that are part of other molecules, so cause agglutination of particular cells or precipitation of glycoconjugates and polysaccharides. Lectins have a role in recognition at the cellular and molecular level and play numerous roles in biological recognition phenomena involving cells, carbohydrates, and proteins. Lectins also mediate attachment and binding of bacteria, viruses, and fungi to their intended targets.
Hemagglutinin esterase (HEs) is a glycoprotein that certain enveloped viruses possess and use as an invading mechanism. HEs helps in the attachment and destruction of certain sialic acid receptors that are found on the host cell surface. Viruses that possess HEs include influenza C virus, toroviruses, and coronaviruses of the subgenus Embecovirus. HEs is a dimer transmembrane protein consisting of two monomers, each monomer is made of three domains. The three domains are: membrane fusion, esterase, and receptor binding domains.
Envelope glycoprotein GP120 is a glycoprotein exposed on the surface of the HIV envelope. It was discovered by Professors Tun-Hou Lee and Myron "Max" Essex of the Harvard School of Public Health in 1984. The 120 in its name comes from its molecular weight of 120 kDa. Gp120 is essential for virus entry into cells as it plays a vital role in attachment to specific cell surface receptors. These receptors are DC-SIGN, Heparan Sulfate Proteoglycan and a specific interaction with the CD4 receptor, particularly on helper T-cells. Binding to CD4 induces the start of a cascade of conformational changes in gp120 and gp41 that lead to the fusion of the viral membrane with the host cell membrane. Binding to CD4 is mainly electrostatic although there are van der Waals interactions and hydrogen bonds.
The terms glycans and polysaccharides are defined by IUPAC as synonyms meaning "compounds consisting of a large number of monosaccharides linked glycosidically". However, in practice the term glycan may also be used to refer to the carbohydrate portion of a glycoconjugate, such as a glycoprotein, glycolipid, or a proteoglycan, even if the carbohydrate is only an oligosaccharide. Glycans usually consist solely of O-glycosidic linkages of monosaccharides. For example, cellulose is a glycan composed of β-1,4-linked D-glucose, and chitin is a glycan composed of β-1,4-linked N-acetyl-D-glucosamine. Glycans can be homo- or heteropolymers of monosaccharide residues, and can be linear or branched.
In molecular biology and biochemistry, glycoconjugates are the classification family for carbohydrates – referred to as glycans – which are covalently linked with chemical species such as proteins, peptides, lipids, and other compounds. Glycoconjugates are formed in processes termed glycosylation.
Siglecs(Sialic acid-binding immunoglobulin-type lectins) are cell surface proteins that bind sialic acid. They are found primarily on the surface of immune cells and are a subset of the I-type lectins. There are 14 different mammalian Siglecs, providing an array of different functions based on cell surface receptor-ligand interactions.
Galectins are a class of proteins that bind specifically to β-galactoside sugars, such as N-acetyllactosamine, which can be bound to proteins by either N-linked or O-linked glycosylation. They are also termed S-type lectins due to their dependency on disulphide bonds for stability and carbohydrate binding. There have been about 15 galectins discovered in mammals, encoded by the LGALS genes, which are numbered in a consecutive manner. Only galectin-1, -2, -3, -4, -7, -7B, -8, -9, -9B, 9C, -10, -12, -13, -14, and -16 have been identified in humans. Galectin-5 and -6 are found in rodents, whereas galectin-11 and -15 are uniquely found in sheep and goats. Members of the galectin family have also been discovered in other mammals, birds, amphibians, fish, nematodes, sponges, and some fungi. Unlike the majority of lectins they are not membrane bound, but soluble proteins with both intra- and extracellular functions. They have distinct but overlapping distributions but found primarily in the cytosol, nucleus, extracellular matrix or in circulation. Although many galectins must be secreted, they do not have a typical signal peptide required for classical secretion. The mechanism and reason for this non-classical secretion pathway is unknown.
Hemagglutinins are homotrimeric glycoproteins present on the protein capsids of viruses in the Paramyxoviridae and Orthomyxoviridae families. Hemagglutinins are responsible for binding to receptors, sialic acid residues, on host cell membranes to initiate virus docking and infection.
In biochemistry, carbohydrate sulfotransferases are enzymes within the class of sulfotransferases which catalyze the transfer of the sulfate functional group to carbohydrate groups in glycoproteins and glycolipids. Carbohydrates are used by cells for a wide range of functions from structural purposes to extracellular communication. Carbohydrates are suitable for such a wide variety of functions due to the diversity in structure generated from monosaccharide composition, glycosidic linkage positions, chain branching, and covalent modification. Possible covalent modifications include acetylation, methylation, phosphorylation, and sulfation. Sulfation, performed by carbohydrate sulfotransferases, generates carbohydrate sulfate esters. These sulfate esters are only located extracellularly, whether through excretion into the extracellular matrix (ECM) or by presentation on the cell surface. As extracellular compounds, sulfated carbohydrates are mediators of intercellular communication, cellular adhesion, and ECM maintenance.
Translational glycobiology or applied glycobiology is the branch of glycobiology and glycochemistry that focuses on developing new pharmaceuticals through glycomics and glycoengineering. Although research in this field presents many difficulties, translational glycobiology presents applications with therapeutic glycoconjugates, with treating various bone diseases, and developing therapeutic cancer vaccines and other targeted therapies. Some mechanisms of action include using the glycan for drug targeting, engineering protein glycosylation for better efficacy, and glycans as drugs themselves.
The National Center for Functional Glycomics is an organization that is focused on the development of technology development in glycosciences. They are specifically focused on glycan analysis and molecular mechanisms of glycan recognition by proteins important in human biology and disease. The center was established at Emory University in 2013 with $5.5 million funding by National Institutes of Health under the leadership of Richard D. Cummings. The center moved to Harvard University in September 2015 and is currently located at Beth Israel Deaconess Medical Center in Boston Massachusetts. The center is affiliated with the Consortium for Functional Glycomics.
The Minimum Information Required About a Glycomics Experiment (MIRAGE) initiative is part of the Minimum Information Standards and specifically applies to guidelines for reporting on a glycomics experiment. The initiative is supported by the Beilstein Institute for the Advancement of Chemical Sciences. The MIRAGE project focuses on the development of publication guidelines for interaction and structural glycomics data as well as the development of data exchange formats. The project was launched in 2011 in Seattle and set off with the description of the aims of the MIRAGE project.
The Symbol Nomenclature For Glycans (SNFG) is a community-curated standard for the depiction of simple monosaccharides and complex carbohydrates (glycans) using various colored-coded, geometric shapes, along with defined text additions. It is hosted by the National Center for Biotechnology Information at the NCBI-Glycans Page. It is curated by an international groups of researchers in the field that are collectively called the SNFG Discussion Group. The overall goal of the SNFG is to:
- Facilitate communications and presentations of monosaccharides and glycans for researchers in the Glycosciences, and for scientists and students less familiar with the field.
- Ensure uniform usage of the nomenclature in the literature, thus helping to ensure scientific accuracy in journal and online publications.
- Continue to develop the SNFG and its applications to aid wider use by the scientific community.
Ten Feizi is a Turkish Cypriot/British molecular biologist who is Professor and Director of the Glycosciences Laboratory at Imperial College London. Her research considers the structure and function of glycans. She was awarded the Society for Glycobiology Rosalind Kornfeld award in 2014. She was also awarded the Fellowship of the Academy of Medical Sciences in 2021.
Glycan-Protein interactions represent a class of biomolecular interactions that occur between free or protein-bound glycans and their cognate binding partners. Intramolecular glycan-protein (protein-glycan) interactions occur between glycans and proteins that they are covalently attached to. Together with protein-protein interactions, they form a mechanistic basis for many essential cell processes, especially for cell-cell interactions and host-cell interactions. For instance, SARS-CoV-2, the causative agent of COVID-19, employs its extensively glycosylated spike (S) protein to bind to the ACE2 receptor, allowing it to enter host cells. The spike protein is a trimeric structure, with each subunit containing 22 N-glycosylation sites, making it an attractive target for vaccine search.
References
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- ↑ Oyelaran O, Gildersleeve JC (Oct 2009). "Glycan arrays: recent advances and future challenges". Curr Opin Chem Biol. 13 (4): 406–413. doi:10.1016/j.cbpa.2009.06.021. PMC 2749919 . PMID 19625207.
- ↑ Mehta, Akul Y; Tilton, Catherine A; Muerner, Lukas; von Gunten, Stephan; Heimburg-Molinaro, Jamie; Cummings, Richard D (14 November 2023). "Reusable glycan microarrays using a microwave assisted wet-erase (MAWE) process". Glycobiology. 34 (2). doi:10.1093/glycob/cwad091. PMC 10969520 . PMID 37962922.
- ↑ Wang D, Carroll GT, Turro NJ, Koberstein JT, Kováč P, Saksena R, Adamo R, Herzenberg LA, Herzenberg LA, Steinman L (2007). "Photogenerated glycan arrays identify immunogenic sugar moieties of Bacillus anthracis exosporium". Proteomics. 7 (2): 180–184. doi: 10.1002/pmic.200600478 . PMID 17205603.
- ↑ Geissner A, Anish C, Seeberger PH (Feb 2014). "Glycan arrays as tools for infectious disease research". Curr Opin Chem Biol. 18: 38–45. doi:10.1016/j.cbpa.2013.11.013. PMID 24534751.
- ↑ Stevens J, Blixt O, Tumpey TM, Taubenberger JK, Paulson JC, Wilson IA (Apr 2006). "Structure and receptor specificity of the hemagglutinin from an H5N1 influenza virus". Science. 312 (5772): 404–410. Bibcode:2006Sci...312..404S. doi:10.1126/science.1124513. PMID 16543414.
- ↑ Childs RA, Palma AS, Wharton S, Matrosovich T, Liu Y, Chai W, Campanero-Rhodes MA, Zhang Y, Eickmann M, Kiso M, Hay A, Matrosovich M, Feizi T (Sep 2009). "Receptor-binding specificity of pandemic influenza A (H1N1) 2009 virus determined by carbohydrate microarray". Nat Biotechnol. 27 (9): 797–799. doi:10.1038/nbt0909-797. PMC 3771066 . PMID 19741625.
- ↑ Wang L, Cummings RD, Smith DF, Huflejt M, Campbell CT, Gildersleeve JC, Gerlach JQ, Kilcoyne M, Joshi L, Serna S, Reichardt NC, Parera Pera N, Pieters RJ, Eng W, Mahal LK (Jun 2014). "Cross-platform comparison of glycan microarray formats". Glycobiology. 24 (6): 507–17. doi:10.1093/glycob/cwu019. PMC 4001710 . PMID 24658466.
- ↑ Horlacher T, Noti C, de Paz JL, Bindschädler P, Hecht ML, Smith DF, Fukuda MN, Seeberger PH (Apr 2011). "Characterization of annexin A1 glycan binding reveals binding to highly sulfated glycans with preference for highly sulfated heparan sulfate and heparin". Biochemistry. 50 (13): 2650–9. doi:10.1021/bi101121a. PMC 3068229 . PMID 21370880.