Glycoproteins are proteins that have carbohydrates (oligosaccharides) covalently attached to their amino acid side chains. These carbohydrate moieties can be attached to the protein through two main types of linkages: N-linked and O-linked glycosylation. In N-linked glycosylation, the carbohydrate is attached to the amide nitrogen of an asparagine residue, while in O-linked glycosylation, it is attached to the hydroxyl oxygen of a serine or threonine residue.
Glycoproteins are widely distributed in living organisms and are involved in various biological processes, including:
- Cell-cell and cell-matrix interactions: Glycoproteins, such as fibronectin, laminin, and selectins, play a critical role in mediating cell adhesion and communication in the extracellular matrix (ECM) and on cell surfaces.
- Signaling and receptor functions: Many cell surface receptors, such as growth factor receptors and cytokine receptors, are glycoproteins that are involved in transmitting signals from the extracellular environment to the interior of the cell.
- Immune system regulation: Glycoproteins play a key role in the immune response, as they are found on the surface of immune cells and are involved in pathogen recognition, cell activation, and inflammation. Examples include immunoglobulins (antibodies) and major histocompatibility complex (MHC) molecules.
- Protein folding and quality control: Glycoproteins like calnexin and calreticulin are involved in protein folding and quality control in the endoplasmic reticulum (ER), ensuring that only correctly folded proteins are transported to their final destinations.
- Structural and mechanical roles: Some glycoproteins, such as mucins, contribute to the structural integrity and mechanical properties of tissues and biological fluids, providing lubrication, hydration, and protection.
- Hormones and enzyme functions: Several hormones, such as human chorionic gonadotropin (hCG) and thyroid-stimulating hormone (TSH), are glycoproteins that regulate various physiological processes. Additionally, some enzymes, like alkaline phosphatase, are glycoproteins with important metabolic functions.
Glycoproteins are synthesized in the endoplasmic reticulum and Golgi apparatus, where the protein backbone is translated, folded, and modified by the addition of carbohydrate chains. The final structure and composition of the carbohydrate moieties on glycoproteins can be highly complex and variable, influencing their stability, solubility, activity, and interaction with other molecules.
Defects in glycoprotein synthesis or processing can lead to various diseases and disorders, such as congenital disorders of glycosylation (CDG), which are a group of inherited metabolic diseases characterized by defects in protein glycosylation pathways.