Journal of Molecular Medicine

, Volume 86, Issue 8, pp 861–874

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

  • Ui-Soon Khoo
  • Kelvin Y. K. Chan
  • Vera S. F. Chan
  • C. L. Steve Lin
Review

DOI: 10.1007/s00109-008-0350-2

Cite this article as:
Khoo, U., Chan, K.Y.K., Chan, V.S.F. et al. J Mol Med (2008) 86: 861. doi:10.1007/s00109-008-0350-2

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.

Keywords

Association studyLectinsInfectionMolecular geneticsPopulation geneticsStructural biology

Supplementary material

109_2008_350_MOESM1_ESM.doc (26 kb)
Supplementary Table 1Frequency distribution of the DC-SIGN −336A/G promoter polymorphism in African, Asian, European, South African colored and Northwestern Colombian populations. (n = number of chromosomes) (DOC 26 kb)
109_2008_350_MOESM2_ESM.doc (406 kb)
Supplementary Fig. 1L-SIGN transfected permissive Vero E6 cells captured/absorbed infectious virus (SARS-CoV) released into the supernatant. Homozygous N7- and heterozygous N7/N5-L-SIGN expressing Vero E6 cells and mock-transfected cells were infected with SARS-CoV. Viral copy number in cell lysates (*) and supernatant (**) for N7-L-SIGN transfected cells was significantly different from that for N5/N7-L-SIGN transfected cells [28]. The N7 and N5 correspond to 7.5 and 5.5 neck-region repeat of L-SIGN according to Feinberg et al. [34]. (DOC 406 kb)
109_2008_350_MOESM3_ESM.doc (26 kb)
Supplementary Fig. 2Allele frequency of the L-SIGN neck-region repeats in different ethnic groups. *Chinese in Hong Kong population reported by Chan et al. [28]; **Chinese in Guangdong population reported by Wang et al. [70]; ***Japanese in Japan reported by Kobayashi et al. [69], and other populations reported by Barreiro et al. [29]. (DOC 26.5 kb)
109_2008_350_MOESM4_ESM.doc (100 kb)
Supplementary Fig. 3Illustration of DC-SIGN and L-SIGN (generated from the HapMap project database). The DC-SIGN and L-SIGN genes are not in linkage disequilibrium with each other as they have separate haplotype blocks. Based on the HapMap data, a recombination hotpot is suggested to be located between these two genes, as indicated by a black color bar (DOC 100 kb)

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Ui-Soon Khoo
    • 1
  • Kelvin Y. K. Chan
    • 1
  • Vera S. F. Chan
    • 2
  • C. L. Steve Lin
    • 2
  1. 1.Department of Pathology, Li Ka Shing Faculty of MedicineThe University of Hong Kong, Queen Mary HospitalHong KongChina
  2. 2.Division of Surgery, Oncology, Reproduction Biology and Anaesthetics, Faculty of MedicineImperial College LondonLondonUK