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Article: DC-SIGN and L-SIGN: The SIGNs for infection
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TitleDC-SIGN and L-SIGN: The SIGNs for infection
 
AuthorsKhoo, US2
Chan, KYK2
Chan, VSF1
Lin, CLS1
 
KeywordsAssociation study
Infection
Lectins
Molecular genetics
Population genetics
Structural biology
 
Issue Date2008
 
CitationJournal 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
 
AbstractTwo 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.
 
ISSN0946-2716
2012 Impact Factor: 4.768
2012 SCImago Journal Rankings: 1.925
 
DOIhttp://dx.doi.org/10.1007/s00109-008-0350-2
 
ISI Accession Number IDWOS:000257945800002
 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorKhoo, US
 
dc.contributor.authorChan, KYK
 
dc.contributor.authorChan, VSF
 
dc.contributor.authorLin, CLS
 
dc.date.accessioned2011-03-28T09:25:21Z
 
dc.date.available2011-03-28T09:25:21Z
 
dc.date.issued2008
 
dc.description.abstractTwo 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.naturelink_to_subscribed_fulltext
 
dc.identifier.citationJournal 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.doihttp://dx.doi.org/10.1007/s00109-008-0350-2
 
dc.identifier.epage874
 
dc.identifier.hkuros145272
 
dc.identifier.isiWOS:000257945800002
 
dc.identifier.issn0946-2716
2012 Impact Factor: 4.768
2012 SCImago Journal Rankings: 1.925
 
dc.identifier.issue8
 
dc.identifier.pmid18458800
 
dc.identifier.scopuseid_2-s2.0-48149094568
 
dc.identifier.spage861
 
dc.identifier.urihttp://hdl.handle.net/10722/132492
 
dc.identifier.volume86
 
dc.languageeng
 
dc.relation.ispartofJournal of Molecular Medicine
 
dc.relation.referencesReferences in Scopus
 
dc.rightsJournal of Molecular Medicine. Copyright © Elsevier Ireland Ltd.
 
dc.subject.meshAlternative Splicing
 
dc.subject.meshAmino Acid Sequence
 
dc.subject.meshAnimals
 
dc.subject.meshCell Adhesion Molecules - chemistry - genetics - physiology
 
dc.subject.meshDendritic Cells - immunology
 
dc.subject.meshDisease Susceptibility - immunology
 
dc.subject.meshHumans
 
dc.subject.meshInfection - genetics
 
dc.subject.meshLectins, C-Type - chemistry - genetics - physiology
 
dc.subject.meshLigands
 
dc.subject.meshModels, Biological
 
dc.subject.meshMolecular Sequence Data
 
dc.subject.meshProtein Isoforms - chemistry - genetics - metabolism
 
dc.subject.meshReceptors, Cell Surface - chemistry - genetics - physiology
 
dc.subjectAssociation study
 
dc.subjectInfection
 
dc.subjectLectins
 
dc.subjectMolecular genetics
 
dc.subjectPopulation genetics
 
dc.subjectStructural biology
 
dc.titleDC-SIGN and L-SIGN: The SIGNs for infection
 
dc.typeArticle
 
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<subject>Population genetics</subject>
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Author Affiliations
  1. Hammersmith Hospital
  2. The University of Hong Kong