Abstract
Glycomics is an up-and-coming field for the life sciences, proposed as a new concept after genomics and proteomics, with a focus on the structure and function of glycans. The purpose of this review is to provide a brief overview of research progress in the vital areas of glycomics, such as functional glycan structure, glycosylation and disease, and to suggest possible new insights for the next field of glycomics.
Glycomics is an up-and-coming field for the life sciences, proposed as a new concept after genomics and proteomics, with a focus on the structure and function of glycans. The purpose of this review is to provide a brief overview of research progress in the vital areas of glycomics, such as functional glycan structure, glycosylation and disease, and to suggest possible new insights for the next field of glycomics.
Keywords: Glycan, Glycomics, Glycosylation, China
Introduction
Related research at home and abroad has carried out in-depth exploration of genomics, proteomics and metabolomics. As a basic macromolecule that constitutes life with lipids, proteins and nucleic acids, carbohydrates can also be defined as glycomics[1]. Glycomics is a new research field after genomics and proteomics. Glycome refers to all sugar chains (including sugar complexes) in cells. Glycomics is a science that studies the expression, regulation and physiological functions of sugar chains. It mainly focuses on the structural analysis of glycoproteins and all glycoproteins involving individual individuals, and determines the mechanism of gene encoding glycoproteins and protein glycosylation[2]. Its basic research part is also called glycobiology[3]. Nucleotide-constituent genes and amino acid-constituent proteins are connected by linear and single combinations. Monosaccharides are always polymerized into glycans, which are connected by multi-site and multi-spatial orientation, resulting in a variety of polymers including linear and branched structures. As a single glucose, it can be polymerized into two completely different structures of amylose and liver glycogen. In addition to storing and providing energy for organisms, there is also a large class of polysaccharides (such as N-glycans or O-glycans) aggregated by a variety of monosaccharides modified on molecules such as nucleic acids, proteins or lipids[4]. Among them, the sugar chains present on the cell surface are covalently linked to cell membrane lipids and proteins, forming a rich dynamic structure on the cell surface. In life activities, glycans cooperate with other three types of biological macromolecules and participate in various physiological and pathological processes of organisms[5].
Polysaccharides constitute an important part of biodiversity due to their complexity and variability. There are about 30,000 to 60,000 genes in the human genome[6]. The human proteome contains more than 1 million proteins ; more than half of the proteins are modified by different glycans, which can produce numerous changes. The blood group H antigen determinant on the surface of red blood cells determines the different ABO blood groups by whether it has terminal N-acetylgalactosamine (GalNAc) or galactose (Gal) residues. The species of various organisms depends on the information-genome of biological systems. Various proteins formed by gene coding constitute the cornerstone of biological functions, and glycans, like buildings built on them, show the diversity of life, regulate and affect physiological and pathological processes. During fertilization, glycans regulate sperm capacitation and sperm-egg recognition[7]; tumor development can be promoted by N-glycan branching structure[4]; glycans and glycan binding proteins can not only regulate immune function, but also mediate the interaction between pathogens and hosts[8]. Because of the special status of glycans and their structural diversity and plasticity, they have become a key factor in biological functional diversity and disease development. The importance and complexity of the role of glycans in life activities have attracted a large number of domestic and foreign scientists to carry out in-depth research, and gradually formed a new discipline-glycomics[9].
Due to the important physiological functions of sugar chains, countries around the world have attached great importance to the related research of glycobiology and invested a lot of manpower and material resources for research[10]. Although glycomics research has attracted much attention in the early years, it has been continuously broken through in recent years due to the development of related technologies[11]. It is worth noting that the development of glycomics in China is very rapid and has gradually led the trend of international research.
Development and status of glycomics
Glycosylation is one of the most common post-translational modifications of proteins. Glycans on proteins play a role in many important biological processes such as cell adhesion, protein folding, molecular transport and clearance, receptor activation and signal transduction[12]. Glycosylation refers to the process of connecting sugar chains with proteins or lipids as substrates under the action of enzymes. As one of the most important protein modification methods in vivo, glycosylation has been studied by more and more teams. Glycosylation modification can regulate the location, diverse functions, activities and lifespan of proteins in cells [13]. Various studies have shown that glycosylation modification can occur on 50% -70% of proteins in cells, and they are involved in various important life activities including cell recognition, cell differentiation, development, signal transduction, and immune response. Abnormal protein glycosylation occurs in many diseases, such as cancer, neurodegenerative diseases, cardiovascular diseases, metabolic diseases, immune diseases and infectious diseases[14, 15]. As a major post-translational modification, glycosylation has a crucial effect on protein function. At present, based on the characteristics of glycosylated proteins, human glycoproteins have been successfully expressed in yeast through glycosylation engineering. Because the glycans of the modified target protein also have the characteristics of uniform structure, large-scale production of glycosylated protein drugs has become possible.
Protein glycosylation is one of the most common post-translational modifications of proteins. It is the process of transferring sugars to proteins under the action of glycosyltransferases and forming glycosidic bonds with special amino acid residues on proteins[16]. According to the differences in binding sites and structures, the sugar chains are divided into the following types:
  1. N-linked glycans (also known as N-glycosylation) attached to amide nitrogen of asparagine (Asn) residues.
  2. O-linked glycans (also known as O-glycosylation) linked to hydroxyl oxygen of serine (Ser) and threonine (Thr) residues.
  3. Sugar chain linked to phosphoric acid on serine phosphate.
  4. C-linked glycans (also known as C-glycosylation, rare) attached to the carbon of Tryptophan (Trp) residues.
  5. Glycosylphosphatidylinositol.
Among the five types of glycans, N-glycosylation is widespread in eukaryotes and is also the most in-depth study of glycosylation.