Galectin

Galectins are a family of proteins defined by their characteristic carbohydrate-recognition domain (CRD) and their binding affinity for β-galactoside sugars. They are found in a wide range of animals, including invertebrates and vertebrates, and some fungi. Unlike many lectins, which are membrane-bound, galectins can be found both inside and outside of cells.

Structure and Function

The defining feature of galectins is their CRD, a conserved amino acid sequence of approximately 130 amino acids. This domain allows galectins to bind specifically to β-galactoside sugars, such as lactose and N-acetyllactosamine. Galectins can exist as monomers or dimers, and some can form higher-order oligomers, influencing their binding affinity and downstream signaling.

Galectins participate in a wide array of biological processes, both intracellularly and extracellularly. Intracellularly, they are involved in pre-mRNA splicing, apoptosis, and cell cycle regulation. Extracellularly, they act as glycan-binding proteins, modulating cell-cell and cell-matrix interactions. They influence processes such as cell adhesion, migration, immune responses, and angiogenesis. The specific functions of galectins often depend on the specific galectin isoform, its oligomeric state, and the cellular context.

Classification

Galectins are classified based on their structural organization. This classification typically includes:

• Proto-type galectins: Contain one CRD and can form non-covalent homodimers. Galectin-1, -2, -5, -7, -10, -11, -13, -14, and -15 belong to this category.
• Tandem-repeat galectins: Contain two CRDs connected by a linker peptide. Galectin-4, -6, -8, -9, and -12 fall into this class.
• Chimera-type galectins: Contain a CRD associated with a non-lectin domain. Galectin-3 is the only known member of this group, possessing an N-terminal domain that mediates oligomerization.

Role in Disease

Dysregulation of galectin expression and function has been implicated in a variety of diseases, including cancer, inflammatory disorders, and infectious diseases. In cancer, galectins can promote tumor growth, metastasis, and immune evasion. In inflammatory diseases, they can contribute to chronic inflammation and tissue damage. Certain galectins are also targeted by pathogens to facilitate infection. Consequently, galectins are being investigated as potential therapeutic targets for various diseases.