2hfg: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
==Crystal structure of hBR3 bound to CB3s-Fab== | ==Crystal structure of hBR3 bound to CB3s-Fab== | ||
<StructureSection load='2hfg' size='340' side='right' caption='[[2hfg]], [[Resolution|resolution]] 2.61Å' scene=''> | <StructureSection load='2hfg' size='340' side='right' caption='[[2hfg]], [[Resolution|resolution]] 2.61Å' scene=''> | ||
| Line 5: | Line 6: | ||
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2hff|2hff]]</td></tr> | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2hff|2hff]]</td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TNFRSF13C, BAFFR, BR3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TNFRSF13C, BAFFR, BR3 ([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=2hfg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hfg OCA], [http://pdbe.org/2hfg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2hfg RCSB], [http://www.ebi.ac.uk/pdbsum/2hfg 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=2hfg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hfg OCA], [http://pdbe.org/2hfg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2hfg RCSB], [http://www.ebi.ac.uk/pdbsum/2hfg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2hfg ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Disease == | == Disease == | ||
| Line 15: | Line 16: | ||
Check<jmol> | Check<jmol> | ||
<jmolCheckbox> | <jmolCheckbox> | ||
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hf/2hfg_consurf.spt"</scriptWhenChecked> | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hf/2hfg_consurf.spt"</scriptWhenChecked> | ||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
</jmolCheckbox> | </jmolCheckbox> | ||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/ | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2hfg ConSurf]. | ||
<div style="clear:both"></div> | <div style="clear:both"></div> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
| Line 32: | Line 33: | ||
==See Also== | ==See Also== | ||
*[[Antibody|Antibody]] | *[[Antibody 3D structures|Antibody 3D structures]] | ||
*[[Tumor necrosis factor receptor|Tumor necrosis factor receptor]] | *[[Tumor necrosis factor receptor|Tumor necrosis factor receptor]] | ||
== References == | == References == | ||
Revision as of 09:56, 27 June 2018
Crystal structure of hBR3 bound to CB3s-FabCrystal structure of hBR3 bound to CB3s-Fab
Structural highlights
Disease[TR13C_HUMAN] Defects in TNFRSF13C are the cause of immunodeficiency common variable type 4 (CVID4) [MIM:613494]; also called antibody deficiency due to BAFFR defect. CVID4 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[TR13C_HUMAN] B-cell receptor specific for TNFSF13B/TALL1/BAFF/BLyS. Promotes the survival of mature B-cells and the B-cell response.[2] [3] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedBR3, which is expressed on all mature B cells, is a specific receptor for the B-cell survival and maturation factor BAFF (B-cell-activating factor belonging to the tumor necrosis factor [TNF] family). In order to investigate the consequences of targeting BR3 in murine models and to assess the potential of BR3 antibodies as human therapeutics, synthetic antibody phage libraries were employed to identify BAFF-blocking antibodies cross-reactive to murine and human BR3, which share 52% identity in their extracellular domains. We found an antibody, CB1, which exhibits muM affinity for murine BR3 and very weak affinity for the human receptor. CB3s, an affinity-matured variant of CB1, has sub-nM affinity for BR3 from both species. Alanine scanning and crystallographic structural analysis of the CB3s/BR3 complex reveal that CB3s mimics BAFF by interacting with a similar region of the BR3 surface. Despite this similarity in binding epitopes, CB1 variants antagonize BAFF-dependent human B-cell proliferation in vitro and are effective at reducing murine B-cell populations in vivo, showing significant promise as therapeutics for human B-cell-mediated diseases. Synthetic anti-BR3 antibodies that mimic BAFF binding and target both human and murine B cells.,Lee CV, Hymowitz SG, Wallweber HJ, Gordon NC, Billeci KL, Tsai SP, Compaan DM, Yin J, Gong Q, Kelley RF, DeForge LE, Martin F, Starovasnik MA, Fuh G Blood. 2006 Nov 1;108(9):3103-11. Epub 2006 Jul 13. PMID:16840730[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||