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3p7f

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Revision as of 13:18, 5 August 2016

Structure of the human Langerin carbohydrate recognition domain

Structural highlights

3p7f is a 4 chain structure with sequence from Human. This structure supersedes the now removed PDB entry 3bbs. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	3p7g, 3p7h
Gene:	CD207, CLEC4K, Leucocyte cDNA (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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]

Publication Abstract from PubMed

Langerin is a type II transmembrane oligosaccharide receptor on Langerhans cells (LCs), a prominent subclass of dendritic cells (DCs) that mediate immune responses in epithelia and play a role in HIV degradation. Its extracellular moiety comprises a neck region with several heptad repeats and an exposed carboxy-terminal calcium-type carbohydrate-recognition domain (CRD). The CRD of human Langerin, which was expressed as a soluble protein in the periplasm of E. coli, was crystallized both alone and in the presence of two sugars, followed by X-ray analyses to resolutions of 2.5A for apo-Langerin and to 1.6A and 2.1A for the complexes with mannose and maltose, respectively. The fold of the Langerin CRD (dubbed LangA) resembles that of other typical C-type lectins such as DC-SIGN. However, especially in the long loop region (LLR), which is responsible for carbohydrate-binding, two additional secondary structure elements are present: a 3(10) helix and a small beta-sheet arising from the extended beta-strand 2, which enters into a hairpin and a new strand beta2'. Unexpectedly, the crystal structures in the presence of maltose and mannose reveal two sugar-binding sites. One is calcium-dependent and structurally conserved in the C-type lectin family whereas the second one represents a novel, calcium-independent type. Based on these data, a model for the binding of mannan, a component of many endogenous as well as viral glycoproteins, is proposed and the differences in binding behavior between Langerin and DC-SIGN with respect to the Lewis X carbohydrate antigen and its derivatives can be explained. Therefore, the crystal structure of LangA should be helpful for the development of new marker reagents selective for LCs and also of therapeutic compounds that may enhance the inhibitory role of Langerin towards HIV infection.

The carbohydrate recognition domain of Langerin reveals high structural similarity with the one of DC-SIGN but an additional, calcium-independent sugar-binding site.,Chatwell L, Holla A, Kaufer BB, Skerra A Mol Immunol. 2008 Apr;45(7):1981-94. Epub 2007 Dec 3. PMID:18061677^[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
↑ Chatwell L, Holla A, Kaufer BB, Skerra A. The carbohydrate recognition domain of Langerin reveals high structural similarity with the one of DC-SIGN but an additional, calcium-independent sugar-binding site. Mol Immunol. 2008 Apr;45(7):1981-94. Epub 2007 Dec 3. PMID:18061677 doi:10.1016/j.molimm.2007.10.030

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3p7f"

@@ Line 1: / Line 1: @@
 ==Structure of the human Langerin carbohydrate recognition domain==
 <StructureSection load='3p7f' size='340' side='right' caption='[[3p7f]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3p7f]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3bbs 3bbs]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3P7F OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3P7F FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3p7f]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3bbs 3bbs]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3P7F OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3P7F 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>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3p7g|3p7g]], [[3p7h|3p7h]]</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CD207, CLEC4K, Leucocyte cDNA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CD207, CLEC4K, Leucocyte cDNA ([http://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=3p7f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3p7f OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3p7f RCSB], [http://www.ebi.ac.uk/pdbsum/3p7f PDBsum]</span></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=3p7f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3p7f OCA], [http://pdbe.org/3p7f PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3p7f RCSB], [http://www.ebi.ac.uk/pdbsum/3p7f PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3p7f ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 20: / Line 21: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3p7f" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Schiefner, A]]
 [[Category: Skerra, A]]

3p7f

From Proteopedia

Revision as of 13:18, 5 August 2016

Structure of the human Langerin carbohydrate recognition domain

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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