Article: DC-SIGN and L-SIGN: The SIGNs for infection
| Title | DC-SIGN and L-SIGN: The SIGNs for infection |
|---|---|
| Authors | Khoo, US2 Chan, KYK2 Chan, VSF1 Lin, CLS1 |
| Keywords | Association study Infection Lectins Molecular genetics Population genetics Structural biology |
| Issue Date | 2008 |
| Citation | Journal Of Molecular Medicine, 2008, v. 86 n. 8, p. 861-874 [How to Cite?] DOI: http://dx.doi.org/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. © 2008 Springer-Verlag. |
| ISSN | 0946-2716 2011 Impact Factor: 4.668 2011 SCImago Journal Rankings: 0.603 |
| DOI | http://dx.doi.org/10.1007/s00109-008-0350-2 |
| ISI Accession Number ID | WOS:000257945800002 |
| References | References in Scopus |
| dc.contributor.author | Khoo, US |
|---|---|
| dc.contributor.author | Chan, KYK |
| dc.contributor.author | Chan, VSF |
| dc.contributor.author | Lin, CLS |
| dc.date.accessioned | 2011-03-28T09:25:21Z |
| dc.date.available | 2011-03-28T09:25:21Z |
| dc.date.issued | 2008 |
| dc.description.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. © 2008 Springer-Verlag. |
| dc.description.nature | link_to_subscribed_fulltext |
| dc.identifier.citation | Journal Of Molecular Medicine, 2008, v. 86 n. 8, p. 861-874 [How to Cite?] DOI: http://dx.doi.org/10.1007/s00109-008-0350-2 |
| dc.identifier.doi | http://dx.doi.org/10.1007/s00109-008-0350-2 |
| dc.identifier.epage | 874 |
| dc.identifier.hkuros | 145272 |
| dc.identifier.isi | WOS:000257945800002 |
| dc.identifier.issn | 0946-2716 2011 Impact Factor: 4.668 2011 SCImago Journal Rankings: 0.603 |
| dc.identifier.issue | 8 |
| dc.identifier.pmid | 18458800 |
| dc.identifier.scopus | eid_2-s2.0-48149094568 |
| dc.identifier.spage | 861 |
| dc.identifier.uri | http://hdl.handle.net/10722/132492 |
| dc.identifier.volume | 86 |
| dc.language | eng |
| dc.relation.ispartof | Journal of Molecular Medicine |
| dc.relation.references | References in Scopus |
| dc.rights | Journal of Molecular Medicine. Copyright © Elsevier Ireland Ltd. |
| dc.subject.mesh | Alternative Splicing |
| dc.subject.mesh | Amino Acid Sequence |
| dc.subject.mesh | Animals |
| dc.subject.mesh | Cell Adhesion Molecules - chemistry - genetics - physiology |
| dc.subject.mesh | Dendritic Cells - immunology |
| dc.subject.mesh | Disease Susceptibility - immunology |
| dc.subject.mesh | Humans |
| dc.subject.mesh | Infection - genetics |
| dc.subject.mesh | Lectins, C-Type - chemistry - genetics - physiology |
| dc.subject.mesh | Ligands |
| dc.subject.mesh | Models, Biological |
| dc.subject.mesh | Molecular Sequence Data |
| dc.subject.mesh | Protein Isoforms - chemistry - genetics - metabolism |
| dc.subject.mesh | Receptors, Cell Surface - chemistry - genetics - physiology |
| dc.subject | Association study |
| dc.subject | Infection |
| dc.subject | Lectins |
| dc.subject | Molecular genetics |
| dc.subject | Population genetics |
| dc.subject | Structural biology |
| dc.title | DC-SIGN and L-SIGN: The SIGNs for infection |
| dc.type | Article |
Author Affiliations
- Hammersmith Hospital
- The University of Hong Kong

