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| | ==Structural tuning of CD81LEL (space group C2)== | | ==Structural tuning of CD81LEL (space group C2)== |
| - | <StructureSection load='5m4r' size='340' side='right' caption='[[5m4r]], [[Resolution|resolution]] 3.10Å' scene=''> | + | <StructureSection load='5m4r' size='340' side='right'caption='[[5m4r]], [[Resolution|resolution]] 3.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5m4r]] is a 5 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5M4R OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5M4R FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5m4r]] is a 5 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=5M4R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5M4R FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 3.1Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5m2c|5m2c]], [[5m3d|5m3d]], [[5m33|5m33]], [[5m3t|5m3t]], [[1g8q|1g8q]], [[1iv5|1iv5]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=5m4r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5m4r OCA], [http://pdbe.org/5m4r PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5m4r RCSB], [http://www.ebi.ac.uk/pdbsum/5m4r PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5m4r 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=5m4r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5m4r OCA], [https://pdbe.org/5m4r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5m4r RCSB], [https://www.ebi.ac.uk/pdbsum/5m4r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5m4r ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/CD81_HUMAN CD81_HUMAN]] Defects in CD81 are the cause of immunodeficiency common variable type 6 (CVID6) [MIM:[http://omim.org/entry/613496 613496]]; also called antibody deficiency due to CD81 defect. CVID6 is a primary immunodeficiency characterized by antibody deficiency, hypogammaglobulinemia, recurrent bacterial infections and an inability to mount an antibody response to antigen. The defect results from a failure of B-cell differentiation and impaired secretion of immunoglobulins; the numbers of circulating B-cells is usually in the normal range, but can be low.<ref>PMID:20237408</ref> | + | [https://www.uniprot.org/uniprot/CD81_HUMAN CD81_HUMAN] Defects in CD81 are the cause of immunodeficiency common variable type 6 (CVID6) [MIM:[https://omim.org/entry/613496 613496]; also called antibody deficiency due to CD81 defect. CVID6 is a primary immunodeficiency characterized by antibody deficiency, hypogammaglobulinemia, recurrent bacterial infections and an inability to mount an antibody response to antigen. The defect results from a failure of B-cell differentiation and impaired secretion of immunoglobulins; the numbers of circulating B-cells is usually in the normal range, but can be low.<ref>PMID:20237408</ref> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CD81_HUMAN CD81_HUMAN]] May play an important role in the regulation of lymphoma cell growth. Interacts with a 16-kDa Leu-13 protein to form a complex possibly involved in signal transduction. May act as the viral receptor for HCV. | + | [https://www.uniprot.org/uniprot/CD81_HUMAN CD81_HUMAN] May play an important role in the regulation of lymphoma cell growth. Interacts with a 16-kDa Leu-13 protein to form a complex possibly involved in signal transduction. May act as the viral receptor for HCV. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 5m4r" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5m4r" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[CD81|CD81]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Abrescia, N G.A]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Cell adhesion]] | + | [[Category: Large Structures]] |
| - | [[Category: Human cellular receptor for hepatitis c virus]] | + | [[Category: Abrescia NG]] |
| | + | [[Category: Cunha ES]] |
| | + | [[Category: Hospital A]] |
| | + | [[Category: Orozco M]] |
| | + | [[Category: Rojas AL]] |
| | + | [[Category: Roversi P]] |
| | + | [[Category: Sfriso P]] |
| Structural highlights
Disease
CD81_HUMAN Defects in CD81 are the cause of immunodeficiency common variable type 6 (CVID6) [MIM:613496; also called antibody deficiency due to CD81 defect. CVID6 is a primary immunodeficiency characterized by antibody deficiency, hypogammaglobulinemia, recurrent bacterial infections and an inability to mount an antibody response to antigen. The defect results from a failure of B-cell differentiation and impaired secretion of immunoglobulins; the numbers of circulating B-cells is usually in the normal range, but can be low.[1]
Function
CD81_HUMAN May play an important role in the regulation of lymphoma cell growth. Interacts with a 16-kDa Leu-13 protein to form a complex possibly involved in signal transduction. May act as the viral receptor for HCV.
Publication Abstract from PubMed
Hepatitis C virus (HCV) enters into human hepatocytes via tetraspanin hCD81. HCV glycoprotein E2 recognizes the "head" subdomain of the large extracellular loop (LEL) of CD81 (hCD81LEL), but the precise mechanism of virus cell attachment and entry remains elusive. Here, by combining the structural analysis of a conspicuous number of crystallized CD81LEL molecules with molecular dynamics simulations, we show that the conformational plasticity of the hCD81LEL head subdomain is a molecular property of the receptor. The observed closed, intermediate, and open conformations of the head subdomain provide distinct binding platforms. Simulations at pH 7.4 and 4.0 indicate that this dynamism is pH modulated. The crystallized double conformation of the disulfide bridge C157-C175 at the base of the head subdomain identifies this bond as the molecular zipper of the plasticity of hCD81LEL. We propose that this conformational dependence of hCD81LEL, which is finely tuned by pH and redox conditions, enables the virus-receptor interactions to diversely re-engage at endosomal conditions.
Mechanism of Structural Tuning of the Hepatitis C Virus Human Cellular Receptor CD81 Large Extracellular Loop.,Cunha ES, Sfriso P, Rojas AL, Hospital A, Orozco M, Abrescia NG Structure. 2016 Nov 21. pii: S0969-2126(16)30343-4. doi:, 10.1016/j.str.2016.11.003. PMID:27916518[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ van Zelm MC, Smet J, Adams B, Mascart F, Schandene L, Janssen F, Ferster A, Kuo CC, Levy S, van Dongen JJ, van der Burg M. CD81 gene defect in humans disrupts CD19 complex formation and leads to antibody deficiency. J Clin Invest. 2010 Apr;120(4):1265-74. doi: 10.1172/JCI39748. Epub 2010 Mar 8. PMID:20237408 doi:10.1172/JCI39748
- ↑ Cunha ES, Sfriso P, Rojas AL, Hospital A, Orozco M, Abrescia NG. Mechanism of Structural Tuning of the Hepatitis C Virus Human Cellular Receptor CD81 Large Extracellular Loop. Structure. 2016 Nov 21. pii: S0969-2126(16)30343-4. doi:, 10.1016/j.str.2016.11.003. PMID:27916518 doi:http://dx.doi.org/10.1016/j.str.2016.11.003
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