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| | <StructureSection load='7wz8' size='340' side='right'caption='[[7wz8]], [[Resolution|resolution]] 6.40Å' scene=''> | | <StructureSection load='7wz8' size='340' side='right'caption='[[7wz8]], [[Resolution|resolution]] 6.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[7wz8]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7WZ8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7WZ8 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7wz8]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7WZ8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7WZ8 FirstGlance]. <br> |
| | </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=7wz8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7wz8 OCA], [https://pdbe.org/7wz8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7wz8 RCSB], [https://www.ebi.ac.uk/pdbsum/7wz8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7wz8 ProSAT]</span></td></tr> | | </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=7wz8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7wz8 OCA], [https://pdbe.org/7wz8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7wz8 RCSB], [https://www.ebi.ac.uk/pdbsum/7wz8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7wz8 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| - | <div style="background-color:#fffaf0;">
| + | == Disease == |
| - | == Publication Abstract from PubMed == | + | [[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> |
| - | Langerhans cells are specialized antigen-presenting cells localized within the epidermis and mucosal epithelium. Upon contact with Langerhans cells, pathogens are captured by the C-type lectin langerin and internalized into a structurally unique vesicle known as a Birbeck granule. Although the immunological role of Langerhans cells and Birbeck granules have been extensively studied, the mechanism by which the characteristic zippered membrane structure of Birbeck granules is formed remains elusive. In this study, we observed isolated Birbeck granules using cryo-electron tomography and reconstructed the 3D structure of the repeating unit of the honeycomb lattice of langerin at 6.4 A resolution. We found that the interaction between the two langerin trimers was mediated by docking the flexible loop at residues 258-263 into the secondary carbohydrate-binding cleft. Mutations within the loop inhibited Birbeck granule formation and the internalization of HIV pseudovirus. These findings suggest a molecular mechanism for membrane zippering during Birbeck granule biogenesis and provide insight into the role of langerin in the defense against viral infection.
| + | == Function == |
| - | | + | [[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> |
| - | Cryo-electron tomography of Birbeck granules reveals the molecular mechanism of langerin lattice formation.,Oda T, Yanagisawa H, Shinmori H, Ogawa Y, Kawamura T Elife. 2022 Jun 27;11. pii: 79990. doi: 10.7554/eLife.79990. PMID:35758632<ref>PMID:35758632</ref>
| + | |
| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div> | + | |
| - | <div class="pdbe-citations 7wz8" style="background-color:#fffaf0;"></div> | + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Oda, T]] | + | [[Category: Oda T]] |
| - | [[Category: Yanagisawa, H]] | + | [[Category: Yanagisawa H]] |
| - | [[Category: Birbeck granule]]
| + | |
| - | [[Category: C-type lectin]]
| + | |
| - | [[Category: Langerhans cell]]
| + | |
| - | [[Category: Membrane protein]]
| + | |
| - | [[Category: Virus defense]]
| + | |
| 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]
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
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