Title |
DC-SIGN and L-SIGN: the SIGNs for infection
|
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Published in |
Journal of Molecular Medicine, May 2008
|
DOI | 10.1007/s00109-008-0350-2 |
Pubmed ID | |
Authors |
Ui-Soon Khoo, Kelvin Y. K. Chan, Vera S. F. Chan, C. L. Steve Lin |
Abstract |
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. |
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Geographical breakdown
Country | Count | As % |
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Brazil | 2 | 2% |
Netherlands | 1 | <1% |
France | 1 | <1% |
South Africa | 1 | <1% |
Canada | 1 | <1% |
Mexico | 1 | <1% |
Unknown | 125 | 95% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 35 | 27% |
Student > Master | 23 | 17% |
Researcher | 22 | 17% |
Student > Bachelor | 8 | 6% |
Other | 8 | 6% |
Other | 16 | 12% |
Unknown | 20 | 15% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 40 | 30% |
Biochemistry, Genetics and Molecular Biology | 21 | 16% |
Immunology and Microbiology | 20 | 15% |
Medicine and Dentistry | 10 | 8% |
Chemistry | 5 | 4% |
Other | 9 | 7% |
Unknown | 27 | 20% |