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| | ==Trimeric Structure of Langerin== | | ==Trimeric Structure of Langerin== |
| - | <StructureSection load='3kqg' size='340' side='right' caption='[[3kqg]], [[Resolution|resolution]] 2.30Å' scene=''> | + | <StructureSection load='3kqg' size='340' side='right'caption='[[3kqg]], [[Resolution|resolution]] 2.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3kqg]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KQG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3KQG FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3kqg]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KQG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3KQG FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CD207, CLEC4K ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CD207, CLEC4K ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3kqg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kqg OCA], [http://pdbe.org/3kqg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3kqg RCSB], [http://www.ebi.ac.uk/pdbsum/3kqg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3kqg ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3kqg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kqg OCA], [https://pdbe.org/3kqg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3kqg RCSB], [https://www.ebi.ac.uk/pdbsum/3kqg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3kqg ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/CLC4K_HUMAN CLC4K_HUMAN]] Defects in CD207 are the cause of Birbeck granule deficiency (BIRGD) [MIM:[http://omim.org/entry/613393 613393]]. It is a condition characterized by the absence of Birbeck granules in epidermal Langerhans cells. Despite the lack of Birbeck granules Langerhans cells are present in normal numbers and have normal morphologic characteristics and antigen-presenting capacity.<ref>PMID:15816828</ref> <ref>PMID:16567809</ref> | + | [[https://www.uniprot.org/uniprot/CLC4K_HUMAN CLC4K_HUMAN]] Defects in CD207 are the cause of Birbeck granule deficiency (BIRGD) [MIM:[https://omim.org/entry/613393 613393]]. It is a condition characterized by the absence of Birbeck granules in epidermal Langerhans cells. Despite the lack of Birbeck granules Langerhans cells are present in normal numbers and have normal morphologic characteristics and antigen-presenting capacity.<ref>PMID:15816828</ref> <ref>PMID:16567809</ref> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CLC4K_HUMAN CLC4K_HUMAN]] Calcium-dependent lectin displaying mannose-binding specificity. Induces the formation of Birbeck granules (BGs); is a potent regulator of membrane superimposition and zippering. Binds to sulfated as well as mannosylated glycans, keratan sulfate (KS) and beta-glucans. Facilitates uptake of antigens and is involved in the routing and/or processing of antigen for presentation to T cells. Major receptor on primary Langerhans cells for Candida species, Saccharomyces species, and Malassezia furfur. Protects against human immunodeficiency virus-1 (HIV-1) infection. Binds to high-mannose structures present on the envelope glycoprotein which is followed by subsequent targeting of the virus to the Birbeck granules leading to its rapid degradation.<ref>PMID:10661407</ref> <ref>PMID:17334373</ref> <ref>PMID:20026605</ref> <ref>PMID:20097424</ref> | + | [[https://www.uniprot.org/uniprot/CLC4K_HUMAN CLC4K_HUMAN]] Calcium-dependent lectin displaying mannose-binding specificity. Induces the formation of Birbeck granules (BGs); is a potent regulator of membrane superimposition and zippering. Binds to sulfated as well as mannosylated glycans, keratan sulfate (KS) and beta-glucans. Facilitates uptake of antigens and is involved in the routing and/or processing of antigen for presentation to T cells. Major receptor on primary Langerhans cells for Candida species, Saccharomyces species, and Malassezia furfur. Protects against human immunodeficiency virus-1 (HIV-1) infection. Binds to high-mannose structures present on the envelope glycoprotein which is followed by subsequent targeting of the virus to the Birbeck granules leading to its rapid degradation.<ref>PMID:10661407</ref> <ref>PMID:17334373</ref> <ref>PMID:20026605</ref> <ref>PMID:20097424</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kq/3kqg_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kq/3kqg_consurf.spt"</scriptWhenChecked> |
| | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Human]] | | [[Category: Human]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Feinberg, H]] | | [[Category: Feinberg, H]] |
| | [[Category: Powlesland, A S]] | | [[Category: Powlesland, A S]] |
| Structural highlights
Disease
[CLC4K_HUMAN] Defects in CD207 are the cause of Birbeck granule deficiency (BIRGD) [MIM:613393]. It is a condition characterized by the absence of Birbeck granules in epidermal Langerhans cells. Despite the lack of Birbeck granules Langerhans cells are present in normal numbers and have normal morphologic characteristics and antigen-presenting capacity.[1] [2]
Function
[CLC4K_HUMAN] Calcium-dependent lectin displaying mannose-binding specificity. Induces the formation of Birbeck granules (BGs); is a potent regulator of membrane superimposition and zippering. Binds to sulfated as well as mannosylated glycans, keratan sulfate (KS) and beta-glucans. Facilitates uptake of antigens and is involved in the routing and/or processing of antigen for presentation to T cells. Major receptor on primary Langerhans cells for Candida species, Saccharomyces species, and Malassezia furfur. Protects against human immunodeficiency virus-1 (HIV-1) infection. Binds to high-mannose structures present on the envelope glycoprotein which is followed by subsequent targeting of the virus to the Birbeck granules leading to its rapid degradation.[3] [4] [5] [6]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Langerin, an endocytic receptor of Langerhans cells, binds pathogens such as human immunodeficiency virus by recognition of surface glycoconjugates and mediates their internalization into Birbeck granules. Langerin has an extracellular region consisting of a C-type carbohydrate-recognition domain (CRD) and a neck region that stabilizes formation of trimers. As in many other C-type lectins, oligomerization is required for high affinity binding to glycan ligands and is also likely to be important for determining specificity. To facilitate structural analysis of the human langerin trimer, a truncated form of the extracellular region, consisting of part of the neck and the CRD, has been characterized. Like the full-length protein, truncated langerin exists as a stable trimer in solution. Glycan array screening with the trimeric fragment shows that high mannose oligosaccharides are the best ligands for langerin. Structural analysis of the trimeric fragment of langerin confirms that the neck region forms a coiled-coil of alpha-helices. Multiple interactions between the neck region and the CRDs make the trimer a rigid unit with the three CRDs in fixed positions and the primary sugar-binding sites separated by a distance of 42 A. The fixed orientation of the sugar-binding sites in the trimer is likely to place constraints on the ligands that can be bound by langerin.
Trimeric structure of langerin.,Feinberg H, Powlesland AS, Taylor ME, Weis WI J Biol Chem. 2010 Apr 23;285(17):13285-93. Epub 2010 Feb 24. PMID:20181944[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Verdijk P, Dijkman R, Plasmeijer EI, Mulder AA, Zoutman WH, Mieke Mommaas A, Tensen CP. A lack of Birbeck granules in Langerhans cells is associated with a naturally occurring point mutation in the human Langerin gene. J Invest Dermatol. 2005 Apr;124(4):714-7. PMID:15816828 doi:10.1111/j.0022-202X.2005.23645.x
- ↑ Ward EM, Stambach NS, Drickamer K, Taylor ME. Polymorphisms in human langerin affect stability and sugar binding activity. J Biol Chem. 2006 Jun 2;281(22):15450-6. Epub 2006 Mar 27. PMID:16567809 doi:10.1074/jbc.M511502200
- ↑ Valladeau J, Ravel O, Dezutter-Dambuyant C, Moore K, Kleijmeer M, Liu Y, Duvert-Frances V, Vincent C, Schmitt D, Davoust J, Caux C, Lebecque S, Saeland S. Langerin, a novel C-type lectin specific to Langerhans cells, is an endocytic receptor that induces the formation of Birbeck granules. Immunity. 2000 Jan;12(1):71-81. PMID:10661407
- ↑ de Witte L, Nabatov A, Pion M, Fluitsma D, de Jong MA, de Gruijl T, Piguet V, van Kooyk Y, Geijtenbeek TB. Langerin is a natural barrier to HIV-1 transmission by Langerhans cells. Nat Med. 2007 Mar;13(3):367-71. Epub 2007 Mar 4. PMID:17334373 doi:10.1038/nm1541
- ↑ Tateno H, Ohnishi K, Yabe R, Hayatsu N, Sato T, Takeya M, Narimatsu H, Hirabayashi J. Dual specificity of Langerin to sulfated and mannosylated glycans via a single C-type carbohydrate recognition domain. J Biol Chem. 2010 Feb 26;285(9):6390-400. doi: 10.1074/jbc.M109.041863. Epub 2009, Dec 21. PMID:20026605 doi:10.1074/jbc.M109.041863
- ↑ de Jong MA, Vriend LE, Theelen B, Taylor ME, Fluitsma D, Boekhout T, Geijtenbeek TB. C-type lectin Langerin is a beta-glucan receptor on human Langerhans cells that recognizes opportunistic and pathogenic fungi. Mol Immunol. 2010 Mar;47(6):1216-25. doi: 10.1016/j.molimm.2009.12.016. Epub 2010, Jan 25. PMID:20097424 doi:10.1016/j.molimm.2009.12.016
- ↑ Feinberg H, Powlesland AS, Taylor ME, Weis WI. Trimeric structure of langerin. J Biol Chem. 2010 Apr 23;285(17):13285-93. Epub 2010 Feb 24. PMID:20181944 doi:10.1074/jbc.M109.086058
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