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| | <StructureSection load='6w12' size='340' side='right'caption='[[6w12]], [[Resolution|resolution]] 2.00Å' scene=''> | | <StructureSection load='6w12' size='340' side='right'caption='[[6w12]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6w12]] is a 1 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=6W12 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6W12 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6w12]] is a 1 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=6W12 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6W12 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A2G:N-ACETYL-2-DEOXY-2-AMINO-GALACTOSE'>A2G</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=SER:SERINE'>SER</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CLEC10A, CLECSF13, CLECSF14, HML ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A2G:N-ACETYL-2-DEOXY-2-AMINO-GALACTOSE'>A2G</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=SER:SERINE'>SER</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=6w12 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6w12 OCA], [https://pdbe.org/6w12 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6w12 RCSB], [https://www.ebi.ac.uk/pdbsum/6w12 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6w12 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=6w12 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6w12 OCA], [https://pdbe.org/6w12 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6w12 RCSB], [https://www.ebi.ac.uk/pdbsum/6w12 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6w12 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/CLC10_HUMAN CLC10_HUMAN]] Probable role in regulating adaptive and innate immune responses. Binds in a calcium-dependent manner to terminal galactose and N-acetylgalactosamine units, linked to serine or threonine. These sugar moieties are known as Tn-Ag and are expressed in a variety of carcinoma cells.<ref>PMID:8598452</ref>
| + | [https://www.uniprot.org/uniprot/CLC10_HUMAN CLC10_HUMAN] Probable role in regulating adaptive and innate immune responses. Binds in a calcium-dependent manner to terminal galactose and N-acetylgalactosamine units, linked to serine or threonine. These sugar moieties are known as Tn-Ag and are expressed in a variety of carcinoma cells.<ref>PMID:8598452</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Birrane, G]] | + | [[Category: Birrane G]] |
| - | [[Category: Gabba, A]] | + | [[Category: Gabba A]] |
| - | [[Category: Luz, J G]] | + | [[Category: Luz JG]] |
| - | [[Category: Murphy, P V]] | + | [[Category: Murphy PV]] |
| - | [[Category: Crd]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| Structural highlights
6w12 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 2Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
CLC10_HUMAN Probable role in regulating adaptive and innate immune responses. Binds in a calcium-dependent manner to terminal galactose and N-acetylgalactosamine units, linked to serine or threonine. These sugar moieties are known as Tn-Ag and are expressed in a variety of carcinoma cells.[1]
Publication Abstract from PubMed
The human macrophage galactose lectin (MGL) is an endocytic type II transmembrane receptor expressed on immature monocyte-derived dendritic cells and activated macrophages and plays a role in modulating the immune system in response to infections and cancer. MGL contains an extracellular calcium-dependent (C-type) carbohydrate recognition domain (CRD) that specifically binds terminal N-acetylgalactosamine glycan residues such as the Tn and sialyl-Tn antigens found on tumor cells, as well as other N- and O-glycans displayed on certain viruses and parasites. Even though the glycan specificity of MGL is known and several binding glycoproteins have been identified, the molecular basis for substrate recognition has remained elusive due to the lack of high-resolution structures. Here we present crystal structures of the MGL CRD at near endosomal pH and in several complexes, which reveal details of the interactions with the natural ligand, GalNAc, the cancer-associated Tn-Ser antigen, and a synthetic GalNAc mimetic ligand. Like the asialoglycoprotein receptor, additional calcium atoms are present and contribute to stabilization of the MGL CRD fold. The structure provides the molecular basis for preferential binding of N-acetylgalactosamine over galactose and prompted the re-evaluation of the binding modes previously proposed in solution. Saturation transfer difference nuclear magnetic resonance data acquired using the MGL CRD and interpreted using the crystal structure indicate a single binding mode for GalNAc in solution. Models of MGL1 and MGL2, the mouse homologues of MGL, explain how these proteins might recognize Lewis(X) and GalNAc, respectively.
Crystal Structure of the Carbohydrate Recognition Domain of the Human Macrophage Galactose C-Type Lectin Bound to GalNAc and the Tumor-Associated Tn Antigen.,Gabba A, Bogucka A, Luz JG, Diniz A, Coelho H, Corzana F, Canada FJ, Marcelo F, Murphy PV, Birrane G Biochemistry. 2021 Mar 16. doi: 10.1021/acs.biochem.1c00009. PMID:33724805[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Suzuki N, Yamamoto K, Toyoshima S, Osawa T, Irimura T. Molecular cloning and expression of cDNA encoding human macrophage C-type lectin. Its unique carbohydrate binding specificity for Tn antigen. J Immunol. 1996 Jan 1;156(1):128-35. PMID:8598452
- ↑ Gabba A, Bogucka A, Luz JG, Diniz A, Coelho H, Corzana F, Canada FJ, Marcelo F, Murphy PV, Birrane G. Crystal Structure of the Carbohydrate Recognition Domain of the Human Macrophage Galactose C-Type Lectin Bound to GalNAc and the Tumor-Associated Tn Antigen. Biochemistry. 2021 Mar 16. doi: 10.1021/acs.biochem.1c00009. PMID:33724805 doi:http://dx.doi.org/10.1021/acs.biochem.1c00009
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