China
Africa
Explore chapters and articles related to this topic
Fibroblast Growth Factors
Published in Jason Kelley, Cytokines of the Lung, 2022
The FGF-5 gene also was identified by screening for genes present in tumors that are able to transform NIH 3T3 cells (Zhan et al., 1988). The gene encodes a 267-amino acid protein. Like INT-2, the central core of the protein has about 50% homology to bFGF, but the NH2-terminal and COOH-terminal sequences are unique. The molecule contains a classic signal sequence and is efficiently secreted. The Mr of the primary translation product is 29.5 kd. Posttranslational processing, including cleavage of the signal sequence, N-linked glycosylation at one site, and possible O-linked glycosylation, yields molecules of 32.5–38.5 kd (Bates et al., 1991).
Biology, Biochemistry and Pathophysiology of the Rantes Chemokine
Published in Richard Horuk, Chemoattractant Ligands and Their Receptors, 2020
Peter J. Nelson, James M. Pattison, Alan M. Krensky
The secreted form of the RANTES protein is composed of 68 amino acids with a predicted molecular mass of 7.8 kDa (Figure 1).9 RANTES is a basic polypeptide (PI ~9.5) (net positive charge at neutral pH) which may facilitate its binding to negatively charged glycosaminoglycan structures on the surface of blood vessels.9 Although the primary amino acid sequence for RANTES lacks an obvious consensus sequence for N-linked glycosylation, native RANTES can undergo O-linked glyc-osylation of serine residues at amino acid positions 4 and 5.10 A functional effect of the O-linked glycosylation of RANTES protein has yet to be determined.
The Development of Improved Therapeutics through a Glycan- “Designer” Approach
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
O-linked glycosylation on the contrary is a dynamically explored field due to its potent role in mammalian pathophysiological processes. O-linked glycosylation is characterized by a covalent attachment of glycan through an oxygen atom. The O-linked consensus is initiated by an attachment of N-Acetylgalactosamine (GalNAc) to Ser/Thre but may also be composed of O-linked β-N-acetylglucosamine; hence, classification of O-glycans is according to their initiating monosaccharide. There are around five classes of O-glycosyl modifications known in mammalian cells, these are: O-N-acetylgalactosamine, O-fucose, O-glucose, O-N -acetylglucosamine and O-mannose. Oligosaccharide attachment is catalyzed by O-glycosyltransferases (OGTs) upon recognition of the Asn-X-Ser/Thr (where X is any amino acid). There are many bacterial glycosyltransferases already employed for in vitro controlled glycosylation, opening very successful field of protein glycoengineering. The glycan polymer may vary in heterogeneity, which makes the prediction of monosaccharide building blocks variable in vivo. Additionally, the extra branching of O-glycans involves multiple glycosyltransferases.
Human carbonic anhydrases and post-translational modifications: a hidden world possibly affecting protein properties and functions
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2020
Anna Di Fiore, Claudiu T. Supuran, Andrea Scaloni, Giuseppina De Simone
Protein O-linked glycosylation is a PTM that involves the chemical linkage of a mono-/polysaccharide molecule to the oxygen atom of S/T residues82. In eukaryotes, it occurs after the protein has been synthesised, and generally takes place in the endoplasmic reticulum (ER) and Golgi apparatus. Different sugars can be introduced in the protein structure; based on their nature, they can affect the protein properties in different ways by changing corresponding stability and regulating activity. O-linked glycans have various physiological functions, such as regulation of cell trafficking in the immune system, recognition of foreign material, control of cell metabolism and provision of 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.
Glycosylation and its implications in breast cancer
Published in Expert Review of Proteomics, 2019
Danielle A. Scott, Richard R. Drake
Alterations in breast cancer mucin-type O-linked glycosylation can result in tumor growth and progression through a variety of mechanisms. In the immune system, changes in mucin-type O-linked glycosylation can produce novel interactions between immune cells and lectins. This is demonstrated through the binding of sialylated glycans to sialic acid-binding immunoglobulin-type lectins (siglecs) on monocytes, macrophages, and NK cells. Examples of this specific mechanism include the binding of sialylated MUC1 to siglec-9 on monocytes and macrophages, the binding of sialylated LacNAc (found on core 1 or core 2 branches) to siglecs-7 on NK cells, and the binding of Tn and sialylated Tn antigens to macrophage galactose-specific lectin on dendritic cells and macrophages. Furthermore, the expression of sialyl Lewisx can result binding to selectins on endothelial cells and various core glycans which can dictate how the cancer cells metastasize and respond to epidermal growth factor (EGF) binding [58,88,100–102]. Sialyl Lewisx antigens on leukocytes can contribute to inflammatory response as a result of their interaction with E-selectin on endothelial cells. Interactions between selectins and sialyl Lewisx glycans are crucial for immune cell trafficking, indicating that the cancer is exploiting a normal cellular process to aid in metastasis [58,102]. This interaction exposes sialyl Lewisx antigens at the cell surface, a mechanism that malignant cells capitalize upon for extravasation from the blood circulation and metastasis [103].
Employing proteomics in the study of antigen presentation: an update
Published in Expert Review of Proteomics, 2018
Sri H. Ramarathinam, Nathan P. Croft, Patricia T. Illing, Pouya Faridi, Anthony W. Purcell
Glycosylation of proteins involves the addition of carbohydrate molecules to amino acids – mostly N- or O-linked glycosylation on N or S/T, respectively. Proteins in eukaryotic cells undergo extensive glycosylation in the endoplasmic reticulum and Golgi complexes with the participation of numerous enzymes that impact localization, protein stability, surface expression and secretion [63]. This presents unique challenges in identification due to the heterogeneity of the glycans (including varying branch and chain lengths) on proteins often resulting in multiple isoforms. Current strategies include enzymatic deglycosylation (EndoH, PNGase-F) in addition to specific enrichment, derivatisation, or manual sequencing [64,65]. Of note, removal of N-glycans using PNGase-F results in the conversion of N to D (resulting in a mass difference of 0.98, i.e. that of deamidation of N as described above). One of the earliest known glycopeptides was described by Engelhard et al. where a HLA-A*02:01 restricted peptide YMD*GTMSQV(N3-glyco to D) was identified using mass spectrometry [66]. Only a handful of studies have identified glycopeptides since, and most of them required manual identification of mass spectra highlighting the challenges involved [67–70].