Glycoproteins are proteins that have complex sugar chains, known as glycans, attached to them through a process called glycosylation. Found throughout the biological world, glycoproteins are present in secreted fluids, on the surfaces of cells, and as integral membrane proteins. They participate in a wide array of biological activities, from cell-to-cell communication to immune responses. The structure of a glycoprotein is directly linked to its function, making the study of its architecture important for scientific research.
What Glycoproteins Are Made Of
Glycoproteins are composite molecules built from a protein and a carbohydrate. The protein part is a polypeptide, which is a chain of amino acids linked together. The specific sequence of these amino acids is dictated by an organism’s genetic code and establishes the fundamental framework of the glycoprotein.
The second component consists of carbohydrates, often referred to as glycans. These are oligosaccharide chains, meaning they are polymers made of multiple sugar units. These glycan chains are covalently bonded to the protein backbone, which alters the protein’s properties, for instance, making it more attracted to water.
Glycoproteins are distinguished from similar molecules like proteoglycans. Proteoglycans are a specific subclass characterized by having very long, unbranched polysaccharide chains called glycosaminoglycans. This distinction highlights the diversity within this family of molecules.
The Structure of Glycan Chains
The carbohydrate, or glycan, portion of a glycoprotein is constructed from individual sugar units called monosaccharides. The most common of these building blocks include:
- Glucose
- Galactose
- Mannose
- Fucose
- Sialic acid
- N-acetylglucosamine
- N-acetylgalactosamine
The specific combination and arrangement of these units contribute to the diversity of glycoprotein structures. These individual monosaccharides are linked together by covalent bonds known as glycosidic bonds.
The formation of these bonds can vary, creating further structural complexity. The connections can differ in their anomeric configuration, resulting in either alpha or beta linkages. They can also attach at different points on the sugar rings, such as 1-4, 1-3, or 1-6 linkages, which dictates the overall shape and properties of the glycan.
A defining feature of glycan chains is their ability to be either linear or branched. This branching creates elaborate, three-dimensional structures that extend from the protein surface. Unlike the linear nature of DNA or proteins, the branching of glycans allows a high density of biological information to be stored in a compact space. This structural diversity is a primary characteristic of glycoproteins and is fundamental to their varied roles.
How Sugars Attach to Proteins (Glycosylation)
The formation of a glycoprotein occurs through a regulated process called glycosylation, where glycan chains are attached to the protein. One of the main ways this happens is through N-linked glycosylation. This process involves the attachment of a glycan to the nitrogen atom of an asparagine amino acid residue on the protein.
This type of linkage only occurs when the asparagine is part of a specific three-amino-acid sequence: asparagine-X-serine or asparagine-X-threonine, where X can be any amino acid except proline. N-linked glycosylation begins in the endoplasmic reticulum, a component within the cell.
Another primary method of attachment is O-linked glycosylation. In this case, the glycan chain is connected to the oxygen atom of a serine or threonine amino acid. This process takes place in a different cellular compartment, the Golgi apparatus. The initial sugar attached in O-linked glycosylation is often simpler than in the N-linked process, and the chains are built one sugar at a time.
The attachment and subsequent modification of these sugar chains are controlled by specialized enzymes. Glycosyltransferases are enzymes that catalyze the formation of the bonds between the sugars and the protein, as well as between the individual sugar units. As the glycoprotein moves through the cell’s secretory pathway, other enzymes, such as glycosidases, may remove sugars, while other glycosyltransferases can add new ones, tailoring the final glycan structure.
Why Glycoprotein Structure Matters
The specific three-dimensional structure of a glycoprotein determines its biological activity. The protein provides a foundation, but it is often the complex and varied glycan chains that mediate interactions with other molecules. This structure-function relationship is central to understanding the many roles these molecules play in biology. The architecture of glycoproteins is a deciding factor in processes from protein folding to the workings of the immune system.
Cell-to-cell recognition and adhesion depend on the glycoproteins present on the cell surface. The unique glycan structures act like molecular identification tags, allowing cells to recognize each other as “self” and to bind together to form tissues. For example, the ABO blood group types are determined by different glycoprotein antigens on the surface of red blood cells.
The immune system relies on glycoproteins. Antibodies, which are proteins that identify and neutralize foreign invaders like bacteria and viruses, are themselves glycoproteins. The attached glycan structures can influence how effectively an antibody can signal to other immune cells.
Many viruses, including SARS-CoV-2, have spike proteins that are heavily glycosylated. These glycans can play a part in how the virus attaches to and enters host cells. The structure of these glycans can also help the virus evade the host’s immune response.