|
|
| (One intermediate revision not shown.) |
| Line 3: |
Line 3: |
| | <StructureSection load='4zrq' size='340' side='right'caption='[[4zrq]], [[Resolution|resolution]] 2.60Å' scene=''> | | <StructureSection load='4zrq' size='340' side='right'caption='[[4zrq]], [[Resolution|resolution]] 2.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4zrq]] is a 4 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=4ZRQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZRQ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4zrq]] is a 4 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=4ZRQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZRQ FirstGlance]. <br> |
| - | </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>, <scene name='pdbligand=CNC:CO-CYANOCOBALAMIN'>CNC</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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]] 2.6Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[4zrp|4zrp]]</div></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>, <scene name='pdbligand=CNC:CO-CYANOCOBALAMIN'>CNC</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TCN2, TC2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), CD320, 8D6A, UNQ198/PRO224 ([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'>[https://proteopedia.org/fgij/fg.htm?mol=4zrq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zrq OCA], [https://pdbe.org/4zrq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zrq RCSB], [https://www.ebi.ac.uk/pdbsum/4zrq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zrq 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=4zrq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zrq OCA], [https://pdbe.org/4zrq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zrq RCSB], [https://www.ebi.ac.uk/pdbsum/4zrq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zrq ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[https://www.uniprot.org/uniprot/TCO2_HUMAN TCO2_HUMAN]] Defects in TCN2 are the cause of transcobalamin II deficiency (TCN2 deficiency) [MIM:[https://omim.org/entry/275350 275350]]. This results in various forms of anemia. [[https://www.uniprot.org/uniprot/CD320_HUMAN CD320_HUMAN]] Methylmalonic aciduria due to transcobalamin receptor defect. The disease is caused by mutations affecting the gene represented in this entry.
| + | [https://www.uniprot.org/uniprot/TCO2_HUMAN TCO2_HUMAN] Defects in TCN2 are the cause of transcobalamin II deficiency (TCN2 deficiency) [MIM:[https://omim.org/entry/275350 275350]. This results in various forms of anemia. |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/TCO2_HUMAN TCO2_HUMAN]] Primary vitamin B12-binding and transport protein. Delivers cobalamin to cells. [[https://www.uniprot.org/uniprot/CD320_HUMAN CD320_HUMAN]] Germinal center-B (GC-B) cells differentiate into memory B-cells and plasma cells (PC) through interaction with T-cells and follicular dendritic cells (FDC). CD320 augments the proliferation of PC precursors generated by IL-10. Receptor for the cellular uptake of transcobalamin bound cobalamin.<ref>PMID:11418631</ref> <ref>PMID:18779389</ref>
| + | [https://www.uniprot.org/uniprot/TCO2_HUMAN TCO2_HUMAN] Primary vitamin B12-binding and transport protein. Delivers cobalamin to cells. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 26: |
Line 25: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Alam, A]] | + | [[Category: Alam A]] |
| - | [[Category: Locher, K P]] | + | [[Category: Locher KP]] |
| - | [[Category: Ldlr-r]]
| + | |
| - | [[Category: Transport protein]]
| + | |
| - | [[Category: Vitamin transporter]]
| + | |
| Structural highlights
Disease
TCO2_HUMAN Defects in TCN2 are the cause of transcobalamin II deficiency (TCN2 deficiency) [MIM:275350. This results in various forms of anemia.
Function
TCO2_HUMAN Primary vitamin B12-binding and transport protein. Delivers cobalamin to cells.
Publication Abstract from PubMed
Cellular uptake of vitamin B12 (cobalamin) requires capture of transcobalamin (TC) from the plasma by CD320, a ubiquitous cell surface receptor of the LDLR family. Here we present the crystal structure of human holo-TC in complex with the extracellular domain of CD320, visualizing the structural basis of the TC-CD320 interaction. The observed interaction chemistry can rationalize the high affinity of CD320 for TC and lack of haptocorrin binding. The in vitro affinity and complex stability of TC-CD320 were quantitated using a solid-phase binding assay and thermostability analysis. Stable complexes with TC were also observed for the disease-causing CD320DeltaE88 mutant and for the isolated LDLR-A2 domain. We also determined the structure of the TC-CD320DeltaE88 complex, which revealed only minor changes compared with the wild-type complex. Finally, we demonstrate significantly reduced in vitro affinity of TC for CD320 at low pH, recapitulating the proposed ligand release during the endocytic pathway.
Structural basis of transcobalamin recognition by human CD320 receptor.,Alam A, Woo JS, Schmitz J, Prinz B, Root K, Chen F, Bloch JS, Zenobi R, Locher KP Nat Commun. 2016 Jul 14;7:12100. doi: 10.1038/ncomms12100. PMID:27411955[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Alam A, Woo JS, Schmitz J, Prinz B, Root K, Chen F, Bloch JS, Zenobi R, Locher KP. Structural basis of transcobalamin recognition by human CD320 receptor. Nat Commun. 2016 Jul 14;7:12100. doi: 10.1038/ncomms12100. PMID:27411955 doi:http://dx.doi.org/10.1038/ncomms12100
|
