Langerin consists of a relatively short intracellular domain and an extracellular domain which consists of a neck-region and a carbohydrate recognition domain (CRD). The intracellular part contains a proline-rich domain (PRD). The neck region consists of alpha-helixes and mediates a formation of langerin homotrimers via a coiled-coil interaction. The homotrimers formation increases avidity and specificity of the antigen.[9]
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]
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 gp120 in HIV-1 envelope via langerin. Subsequently, the virus is internalised into the Birbeck granule where it’s degraded and processed for presentation. Thus, langerin has an antiviral activity and protects the cell against HIV-1 infection. If langerin is defect or titres of the virus are too high, the HIV-1 infection may happen.[9][11][12]
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]
^Turville S, Wilkinson J, Cameron P, Dable J, Cunningham AL (November 2003). "The role of dendritic cell C-type lectin receptors in HIV pathogenesis". Journal of Leukocyte Biology. 74 (5): 710–8. doi:10.1189/jlb.0503208. PMID12960229. S2CID44539239.
^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. doi:10.1038/nm1541. PMID17334373. S2CID5090679.
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. doi:10.1385/IR:28:2:93. PMID14610287. S2CID37296843.
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. doi:10.1038/nm1541. PMID17334373. S2CID5090679.
