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:
- N-linked glycans (also known as N-glycosylation) attached to amide
nitrogen of asparagine (Asn) residues.
- O-linked glycans (also known as O-glycosylation) linked to hydroxyl
oxygen of serine (Ser) and threonine (Thr) residues.
- Sugar chain linked to phosphoric acid on serine phosphate.
- C-linked glycans (also known as C-glycosylation, rare) attached to the
carbon of Tryptophan (Trp) residues.
- Glycosylphosphatidylinositol.
Among the five types of glycans, N-glycosylation is widespread in
eukaryotes and is also the most in-depth study of glycosylation.