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
2011 Impact Factor: 4.668
2011 SCImago Journal Rankings: 0.603
DOIhttp://dx.doi.org/10.1007/s00109-008-0350-2
ISI Accession Number IDWOS:000257945800002
ReferencesReferences in Scopus
DC Field
Value
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
2011 Impact Factor: 4.668
2011 SCImago Journal Rankings: 0.603
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
Author Affiliations
  1. Hammersmith Hospital
  2. The University of Hong Kong