C-type lectin

PDB 1jzn EBI

C-type lectin refers to a type of carbohydrate-binding protein domain known as a lectin. The "C-type" stands for "calcium-dependent," indicating that these proteins require calcium ions to bind to carbohydrates. C-type lectins are involved in a variety of cellular functions including cell-cell adhesion, immune response to pathogens, and the clearance of glycoproteins from the cell surface. They are found in a wide range of organisms, from viruses and bacteria to plants and animals, highlighting their importance in both health and disease.

Structure

C-type lectins are characterized by their conserved carbohydrate recognition domain (CRD), which typically binds to specific sugar moieties in a calcium-dependent manner. The CRD can vary in length from about 120 to 150 amino acids and is responsible for the specific binding properties of the lectin. The structural fold of the CRD is stabilized by two conserved disulfide bonds, and the presence of calcium is essential for maintaining the structural integrity necessary for carbohydrate binding.

Classification

C-type lectins are classified into several groups based on their structure and function. The two main categories are:

1. Collectins: These are involved in the recognition of carbohydrate patterns on the surface of pathogens, facilitating their clearance by the immune system. Examples include mannose-binding lectin (MBL) and surfactant proteins A and D (SP-A and SP-D), which play critical roles in innate immunity.
2. Selectins: These are involved in cell-cell interactions and play crucial roles in the inflammatory process by mediating the adhesion of white blood cells to the endothelium. Examples include E-selectin, L-selectin, and P-selectin.

Other subtypes include endocytic receptors, which are involved in the clearance of glycoproteins from the cell surface, and proteoglycans, which are part of the extracellular matrix and cell surface.

Function

C-type lectins play a pivotal role in the immune system. They recognize specific carbohydrate structures found on the surface of pathogens, such as bacteria, viruses, and fungi, leading to their opsonization and clearance by phagocytic cells. This recognition is crucial for the activation of the innate immune response and the subsequent activation of the adaptive immune response.

In addition to their role in immunity, C-type lectins are involved in cell-cell adhesion processes, such as during the inflammatory response when selectins mediate the tethering and rolling of leukocytes on the vascular endothelium. They also play roles in the regulation of cell growth and differentiation, as well as in the clearance of apoptotic cells and cancer surveillance.

Clinical Significance

Alterations in the expression or function of C-type lectins can lead to a variety of diseases. For example, deficiencies in mannose-binding lectin are associated with increased susceptibility to infections, particularly in children. On the other hand, aberrant expression of selectins has been implicated in the pathogenesis of chronic inflammatory diseases and cancer metastasis.

Given their crucial role in the immune response and disease, C-type lectins are of significant interest as potential therapeutic targets. Inhibitors or antagonists of selectins, for example, are being explored as treatments for inflammatory diseases and cancer.

Research Directions

Research in the field of C-type lectins continues to explore their structure-function relationships, mechanisms of carbohydrate recognition, and their roles in health and disease. Understanding the intricate details of how C-type lectins interact with their ligands and how these interactions can be modulated holds promise for the development of novel therapeutic strategies against a wide range of diseases.