What Protein Glycosylation Is
Proteins are complex molecules performing diverse roles, from structural support to facilitating chemical reactions. For proper function, they often undergo modifications after synthesis. Protein glycosylation is one significant modification, involving the enzymatic attachment of carbohydrate chains, or glycans, to a protein molecule.
Proteins modified this way are called glycoproteins. This modification is not rare; it is a widespread and fundamental biological process. Over half of all mammalian proteins are estimated to be glycosylated, highlighting its pervasive nature. Glycosylation “decorates” proteins, adding diverse sugar structures that influence their final shape, stability, and interactions.
How Glycosylation Occurs
Protein glycosylation primarily occurs through two mechanisms: N-linked and O-linked glycosylation. These processes differ in glycan attachment sites and cellular compartments involved. Both types of glycosylation primarily occur within specialized cellular compartments: the endoplasmic reticulum (ER) and the Golgi apparatus, which are responsible for protein processing and transport.
N-linked glycosylation attaches a glycan to the nitrogen atom of an asparagine residue. This process typically begins in the endoplasmic reticulum (ER) as the protein is synthesized, where a pre-assembled sugar structure is transferred. The protein then moves to the Golgi apparatus for further carbohydrate chain refinement.
In contrast, O-linked glycosylation attaches a glycan to the oxygen atom of a serine or threonine residue. This type predominantly occurs in the Golgi apparatus, though some forms begin in the ER. Unlike N-linked glycosylation, O-linked glycosylation typically happens after protein synthesis, involving the sequential addition of individual sugar units.
Key Roles of Glycosylation
Glycans attached to proteins perform many important biological functions. They contribute to protein folding and stability, helping proteins achieve their correct three-dimensional shapes and protecting them from degradation. This ensures their functionality and contributes to their overall integrity and longevity.
Glycosylation also plays a role in cell-to-cell recognition and communication. Glycan patterns on cell surfaces act as molecular identification tags, enabling cells to recognize and interact, crucial for processes like cell adhesion. These modifications also help cells distinguish between healthy cells and foreign invaders.
Glycosylation is also important for immune system function. Many immune molecules, including antibodies, are glycoproteins whose glycans influence interactions with pathogens and other immune cells. For example, glycans on red blood cells determine blood type (A, B, AB, or O), recognized by the immune system to prevent transfusion reactions.
Glycosylation in Health and Illness
Changes in protein glycosylation patterns have implications for human health. Abnormal glycosylation is associated with various diseases, underscoring its role in normal bodily functions. For instance, congenital disorders of glycosylation (CDGs) arise from defects in the glycosylation machinery, affecting multiple organ systems.
Alterations in glycosylation are also observed in cancer and inflammatory diseases. In cancer, changes in cell surface glycans can promote tumor growth, spread, and immune evasion. Similarly, modified glycosylation patterns contribute to the inflammatory response, providing insights into disease mechanisms.
Insights into glycosylation are also important for developing new treatments, particularly therapeutic antibodies. Many biologic drugs, like monoclonal antibodies used in cancer therapy, are glycoproteins. Modifying their glycosylation can improve effectiveness, stability, and duration of activity in the body.