DC-SIGN and L-SIGN: the SIGNs for infection

• Published in: Journal of molecular medicine (Berlin, Germany) Vol. 86; no. 8; pp. 861 - 874
• Main Authors: Khoo, Ui-Soon, Chan, Kelvin Y. K., Chan, Vera S. F., Lin, C. L. Steve
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.08.2008; Springer; Springer Nature B.V
• Subjects: Alternative Splicing; Amino Acid Sequence; Animals; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cell adhesion molecules; Cell Adhesion Molecules - chemistry; Cell Adhesion Molecules - genetics; Cell Adhesion Molecules - physiology; DC-SIGN protein; Dendritic cells; Dendritic Cells - immunology; Disease Susceptibility - immunology; Gene polymorphism; General aspects; Human Genetics; Humans; Infections - genetics; Infectious diseases; Internal Medicine; Lectins; Lectins, C-Type - chemistry; Lectins, C-Type - genetics; Lectins, C-Type - physiology; Ligands; Lymph nodes; Medical sciences; Minority & ethnic groups; Models, Biological; Molecular Medicine; Molecular Sequence Data; Oligomerization; Pathogens; Protein Isoforms - chemistry; Protein Isoforms - genetics; Protein Isoforms - metabolism; Public health; Receptor mechanisms; Receptors, Cell Surface - chemistry; Receptors, Cell Surface - genetics; Receptors, Cell Surface - physiology; Review; Infection; Association study; Lectins; Molecular genetics; Population genetics; Structural biology; Medicine; Association; Infection . Molecular genetics Population genetics Structural biology; Molecular biology; Lectin DC-SIGN; Association study Lectins
• ISSN: 0946-2716; 1432-1440
• DOI: 10.1007/s00109-008-0350-2

Two closely related trans -membrane C-type lectins dendritic cell-specific intracellular adhesion molecules (ICAM)-3 grabbing non-integrin (DC-SIGN or CD209 ) and liver/lymph node-specific ICAM-3 grabbing non-integrin (L-SIGN also known as DC-SIGNR , CD209L or CLEC4M ) directly recognize a wide range of micro-organisms of major impact on public health. Both genes have long been considered to share similar overall structure and ligand-binding characteristics. This review presents more recent biochemical and structural studies, which show that they have distinct ligand-binding properties and different physiological functions. Of importance in both these genes is the presence of an extra-cellular domain consisting of an extended neck region encoded by tandem repeats that support the carbohydrate-recognition domain, which plays a crucial role in influencing the pathogen-binding properties of these receptors. The notable difference between these two genes is in this extra-cellular domain. Whilst the tandem-neck-repeat region remains relatively constant size for DC-SIGN, there is considerable polymorphism for L-SIGN. Homo-oligomerization of the neck region of L-SIGN has been shown to be important for high-affinity ligand binding, and heterozygous expression of the polymorphic variants of L-SIGN in which neck lengths differ could thus affect ligand-binding affinity. Functional studies on the effect of this tandem-neck-repeat region on pathogen-binding, as well as genetic association studies for various infectious diseases and among different populations, are discussed. Worldwide demographic data of the tandem-neck-repeat region showing distinct differences in the neck-region allele and genotype distribution among different ethnic groups are presented. These findings support the neck region as an excellent candidate acting as a functional target for selective pressures exerted by pathogens.