Langerin
| CD207 | |||
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| Location (UCSC) | Chr 2: 70.83 – 70.84 Mb | Chr 6: 83.65 – 83.65 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
| View/Edit Human | View/Edit Mouse |
Langerin (CD207) is a type II transmembrane protein which is encoded by the CD207 gene in humans.[5][6] It was discovered by scientists Sem Saeland and Jenny Valladeau as a main part of Birbeck granules. Langerin is C-type lectin receptor on Langerhans cells (LCs) and in mice also on dermal interstitial CD103+ dendritic cells (DC) and on resident CD8+ DC in lymph nodes.[6][7][8]
Structure
Langerin consists of a relatively short intracellular domain and an extracellular domain which consists of a neck-region and a
The CRD of langerin is similar to CRDs of other C-type lectins. It contains an EPN motif – a Glu-Pro-Asn rich region. The CRD is divided into two lobes by 2 anti-parallel beta-sheets. The upper lobe creates the primary Ca2+ dependent carbohydrates binding site.[9] In contrast to other lectins, for instance, DC-SIGN / DC-SIGNR and MBP, langerin has only one binding site for Ca2+.[5] In the upper lobe, there have been discovered two other binding sites by a crystallization method. These sites are not dependent on Ca2+ and their relation to the primary binding site is not completely understood. All the binding sites are flanked by positively charged amino acids (K299 and K313) which enable binding of negatively charged sulphated carbohydrates. These amino acids are not present in DC-SIGN.[9]
Function
Langerin is expressed in LCs which are located in the
It seems an intracellular Src homology domain of langerin is important for the formation of Birbeck granules. These organelles contain Rab11a which is a molecule participating in langerin recycling.[9]
Langerin has similar function and structure as a DCs surface protein DC-SIGN (CD209). Both receptors bind similar antigens via the CRD, for instance Mycobacterium tuberculosis and HIV-1. However, whereas HIV-1 binding to langerin leads to the elimination of the virus, HIV-1 binding to DC-SIGN leads to infection of the cell.[9]
Clinical significance
In human vaginal mucosa, LCs bind the strongly glycosylated glycoprotein
Langerin also binds mannose, which is in the outer membrane of fungi, and beta-glucans in membrane folds of fungi. By this way, LCs can protect themselves against pathogens like Candida, Saccharomyces and Malassezia furfur. Furthermore, langerin recognizes Gal-6-sulfated lactosamine of glioblastoma.[9][13] In the respiratory epithelium, LCs recognize measles virus via langerin and then, they degrade it and present it to CD4+ T-cells.[13]
Polymorphism
Single nucleotide polymorphism (SNP) in langerin gene may affect the stability as well as the affinity of the protein for some carbohydrates. The most common polymorphism is a replacement of alanine for valine in the 278. position (rs741326). Allelic frequency of this polymorphism is up to 48 %, but it probably does not have any influence on stability and affinity of langerin. Substitution of asparagine for aspartic acid in the 288. position leads to 10-fold reduction in the ability to recognize mannose-BSA. A substitution of tryptophane for arginine in the 264. position leads to a loss of Birbeck granules.[9]
See also
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000116031 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000034783 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ PMID 19175323.
- ^ PMID 10661407.
- PMID 21952811.
- PMID 11777972.
- ^ S2CID 28586402.
- PMID 29449841.
- S2CID 44539239.
- S2CID 5090679.
- ^ PMID 21952811.
Further reading
- Valladeau J, Dezutter-Dambuyant C, Saeland S (2003). "Langerin/CD207 sheds light on formation of birbeck granules and their possible function in Langerhans cells". Immunologic Research. 28 (2): 93–107. S2CID 37296843.
- Quaranta MG, Mattioli B, Giordani L, Viora M (November 2006). "The immunoregulatory effects of HIV-1 Nef on dendritic cells and the pathogenesis of AIDS". FASEB Journal. 20 (13): 2198–208. S2CID 3111709.
- The Sanger Centre, The Washington University Genome Sequencing Center (November 1998). "Toward a complete human genome sequence". Genome Research. 8 (11): 1097–108. PMID 9847074.
- Valladeau J, Ravel O, Dezutter-Dambuyant C, Moore K, Kleijmeer M, Liu Y, et al. (January 2000). "Langerin, a novel C-type lectin specific to Langerhans cells, is an endocytic receptor that induces the formation of Birbeck granules". Immunity. 12 (1): 71–81. PMID 10661407.
- Turville SG, Cameron PU, Handley A, Lin G, Pöhlmann S, Doms RW, Cunningham AL (October 2002). "Diversity of receptors binding HIV on dendritic cell subsets". Nature Immunology. 3 (10): 975–83. S2CID 41018834.
- Hunger RE, Sieling PA, Ochoa MT, Sugaya M, Burdick AE, Rea TH, et al. (March 2004). "Langerhans cells utilize CD1a and langerin to efficiently present nonpeptide antigens to T cells". The Journal of Clinical Investigation. 113 (5): 701–8. PMID 14991068.
- Vashishta A, Fusek M, Vetvicka V (2005). "Possible role of procathepsin D in human cancer". Folia Microbiologica. 50 (1): 71–6. S2CID 25161353.
- Verdijk P, Dijkman R, Plasmeijer EI, Mulder AA, Zoutman WH, Mieke Mommaas A, Tensen CP (April 2005). "A lack of Birbeck granules in Langerhans cells is associated with a naturally occurring point mutation in the human Langerin gene". The Journal of Investigative Dermatology. 124 (4): 714–7. PMID 15816828.
- Bousarghin L, Hubert P, Franzen E, Jacobs N, Boniver J, Delvenne P (May 2005). "Human papillomavirus 16 virus-like particles use heparan sulfates to bind dendritic cells and colocalize with langerin in Langerhans cells". The Journal of General Virology. 86 (Pt 5): 1297–1305. PMID 15831940.
- He B, Qiao X, Klasse PJ, Chiu A, Chadburn A, Knowles DM, et al. (April 2006). "HIV-1 envelope triggers polyclonal Ig class switch recombination through a CD40-independent mechanism involving BAFF and C-type lectin receptors". Journal of Immunology. 176 (7): 3931–41. PMID 16547227.
- Ward EM, Stambach NS, Drickamer K, Taylor ME (June 2006). "Polymorphisms in human langerin affect stability and sugar binding activity". The Journal of Biological Chemistry. 281 (22): 15450–6. PMID 16567809.
- de Witte L, Nabatov A, Pion M, Fluitsma D, de Jong MA, de Gruijl T, et al. (March 2007). "Langerin is a natural barrier to HIV-1 transmission by Langerhans cells". Nature Medicine. 13 (3): 367–71. S2CID 5090679.
- Kaplan DH, Li MO, Jenison MC, Shlomchik WD, Flavell RA, Shlomchik MJ (October 2007). "Autocrine/paracrine TGFbeta1 is required for the development of epidermal Langerhans cells". The Journal of Experimental Medicine. 204 (11): 2545–52. PMID 17938236.
External links
- CD207 protein, human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- Overview of all the structural information available in the PDB for UniProt: Q9UJ71 (C-type lectin domain family 4 member K) at the PDBe-KB.