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Mannose is a sugar monomer of the aldohexose series of carbohydrates. It is a C-2 epimer of glucose. Mannose is important in human metabolism, especially in the glycosylation of certain proteins. Several congenital disorders of glycosylation are associated with mutations in enzymes involved in mannose metabolism.
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.
If terminal sialic acid residues are removed from glycoproteins, the resulting proteins are known as asialoglycoproteins.
Concanavalin A (ConA) is a lectin originally extracted from the jack-bean. It is a member of the legume lectin family. It binds specifically to certain structures found in various sugars, glycoproteins, and glycolipids, mainly internal and nonreducing terminal α-D-mannosyl and α-D-glucosyl groups. Its physiological function in plants, however, is still unknown. ConA is a plant mitogen, and is known for its ability to stimulate mouse T-cell subsets giving rise to four functionally distinct T cell populations, including precursors to regulatory T cells; a subset of human suppressor T-cells is also sensitive to ConA. ConA was the first lectin to be available on a commercial basis, and is widely used in biology and biochemistry to characterize glycoproteins and other sugar-containing entities on the surface of various cells. It is also used to purify glycosylated macromolecules in lectin affinity chromatography, as well as to study immune regulation by various immune cells.
Gilbert Ashwell was an American biochemist at the National Institutes of Health. He was elected as a member of the National Academy of Sciences for his work with Anatol Morell in isolating the first cell receptor.
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.
Convulxin is a snake venom toxin found in a tropical rattlesnake known as Crotalus durissus terrificus. It belongs to the family of hemotoxins, which destroy red blood cells or, as is the case with convulxin, induce blood coagulation.
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.
Langerin (CD207) is a type II transmembrane protein which is encoded by the CD207 gene in humans. It was discovered by scientists Sem Saeland and Jenny Valladeau as a main part of Birbeck granules. Langerin is C-type lectin receptor on Langerhans cells (LCs) and in mice also on dermal interstitial CD103+ dendritic cells (DC) and on resident CD8+ DC in lymph nodes.
The mannose receptor is a C-type lectin primarily present on the surface of macrophages, immature dendritic cells and liver sinusoidal endothelial cells, but is also expressed on the surface of skin cells such as human dermal fibroblasts and keratinocytes. It is the first member of a family of endocytic receptors that includes Endo180 (CD280), M-type PLA2R, and DEC-205 (CD205).
Polysialic acid is an unusual posttranslational modification that occurs on neural cell adhesion molecules (NCAM). Polysialic acid is considerably anionic. This strong negative charge gives this modification the ability to change the protein's surface charge and binding ability. In the synapse, polysialation of NCAM prevents its ability to bind to NCAMs on the adjacent membrane.
C-type lectin domain family 10 member A (CLEC10A) also designated as CD301 is a protein that in humans is encoded by the CLEC10A gene. CLEC10A is part of the C-type lectin superfamily and binds to N-Acetylgalactosamine (GalNAc). It is mainly expressed on myeloid cells and also on oocytes and very early stages of embryogenesis. CLEC10A is used as a marker of the CD1c+ dendritic cell subgroup, also called cDC2. The actions of CLEC10A are diverse, depending on the ligand and environment.
Carbohydrate–protein interactions are the intermolecular and intramolecular interactions between protein and carbohydrate moieties. These interactions form the basis of specific recognition of carbohydrates by lectins. Carbohydrates are important biopolymers and have a variety of functions. Often carbohydrates serve a function as a recognition element. That is, they are specifically recognized by other biomolecules. Proteins which bind carbohydrate structures are known as lectins. Compared to the study of protein–protein and protein–DNA interaction, it is relatively recent that scientists get to know the protein–carbohydrate binding.
Feline coronavirus (FCoV) is a positive-stranded RNA virus that infects cats worldwide. It is a coronavirus of the species Alphacoronavirus 1 which includes canine coronavirus (CCoV) and porcine transmissible gastroenteritis coronavirus (TGEV). It has two different forms: feline enteric coronavirus (FECV) that infects the intestines and feline infectious peritonitis virus (FIPV) that causes the disease feline infectious peritonitis (FIP).
O-linked glycosylation is the attachment of a sugar molecule to the oxygen atom of serine (Ser) or threonine (Thr) residues in a protein. O-glycosylation is a post-translational modification that occurs after the protein has been synthesised. In eukaryotes, it occurs in the endoplasmic reticulum, Golgi apparatus and occasionally in the cytoplasm; in prokaryotes, it occurs in the cytoplasm. Several different sugars can be added to the serine or threonine, and they affect the protein in different ways by changing protein stability and regulating protein activity. O-glycans, which are the sugars added to the serine or threonine, have numerous functions throughout the body, including trafficking of cells in the immune system, allowing recognition of foreign material, controlling cell metabolism and providing cartilage and tendon flexibility. Because of the many functions they have, changes in O-glycosylation are important in many diseases including cancer, diabetes and Alzheimer's. O-glycosylation occurs in all domains of life, including eukaryotes, archaea and a number of pathogenic bacteria including Burkholderia cenocepacia, Neisseria gonorrhoeae and Acinetobacter baumannii.
Asialoglycoprotein receptor 1 is a protein that in humans is encoded by the ASGR1 gene.
Volkensin is a eukaryotic ribosome-inactivating protein found in the Adenia volkensii plant. It is a glycoprotein with two subunits A and B. A subunit is linked to B subunit with disulfide bridges and non-covalent bonds. B subunit is responsible for binding to the galactosyl-terminated receptors on the cell membrane that allows the entry the A subunit of the toxin into the cell, which performs the inhibitory function. Volkensin is a galactose specific lectin that can inhibit protein synthesis in whole cells and in cell-free lysates. This protein can be included into the category of risin like toxins and it resembles modeccin, the toxin of Adenia digitata. Although very similar in composition, volkensin contains more cysteine residues and more than twice as much sugar than modeccin, due to high content of galactose and mannose. In addition, volkensin is able to inhibit protein synthesis at concentrations 10 times lower than required for modeccin. From gene sequencing analysis, volkensin was found to be coded by 1569-bp ORF, that is 523 amino acid residues without introns. The internal linker sequence is 45 bp. The active site of the A subunit contains Ser203, a novel residue that is conserved in all ribosome inactivating proteins.
Modeccin is a toxic lectin, a group of glycoproteins capable of binding specifically to sugar moieties. Different toxic lectins are present in seeds of different origin. Modeccin is found in the roots of the African plant Adenia digitata. These roots are often mistaken for edible roots, which has led to some cases of intoxication. Sometimes the fruit is eaten, or a root extract is drunk as a manner of suicide.
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
- 1 2 3 4 5 Gupta GS (2012). Gupta GS (ed.). Animal Lectins: Form, Function and Clinical Applications. Wien: Springer-Verlag. doi:10.1007/978-3-7091-1065-2. ISBN 978-3-7091-1064-5. S2CID 39053151.
- 1 2 3 "ASGR1 Tissue". Human Protein Atlas.
- ↑ "ASGR1 Cell Lines". Human Protein Atlas.
- ↑ Roggenbuck D, Mytilinaiou MG, Lapin SV, Reinhold D, Conrad K (December 2012). "Asialoglycoprotein receptor (ASGPR): a peculiar target of liver-specific autoimmunity". Auto- Immunity Highlights. 3 (3): 119–125. doi:10.1007/s13317-012-0041-4. PMC 4389076 . PMID 26000135.
- ↑ Harris RL, van den Berg CW, Bowen DJ (2012-08-02). "ASGR1 and ASGR2, the Genes that Encode the Asialoglycoprotein Receptor (Ashwell Receptor), Are Expressed in Peripheral Blood Monocytes and Show Interindividual Differences in Transcript Profile". Molecular Biology International. 2012: 283974. doi: 10.1155/2012/283974 . PMC 3419429 . PMID 22919488.
- ↑ Morell, Anatol G.; Irvine, Ronald A.; Sternlieb, Irmin; Scheinberg, I. Herbert; Ashwell, Gilbert (1968-01-10). "Physical and Chemical Studies on Ceruloplasmin: V. METABOLIC STUDIES ON SIALIC ACID-FREE CERULOPLASMIN IN VIVO". Journal of Biological Chemistry. 243 (1): 155–159. doi: 10.1016/S0021-9258(18)99337-3 . ISSN 0021-9258. PMID 5635941.
