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2hfg

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Revision as of 08:44, 16 January 2015

Crystal structure of hBR3 bound to CB3s-Fab

Structural highlights

2hfg is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	2hff
Gene:	TNFRSF13C, BAFFR, BR3 (Homo sapiens)
Resources:	FirstGlance, OCA, RCSB, PDBsum

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 PubMed

BR3, 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.

References

↑ Warnatz K, Salzer U, Rizzi M, Fischer B, Gutenberger S, Bohm J, Kienzler AK, Pan-Hammarstrom Q, Hammarstrom L, Rakhmanov M, Schlesier M, Grimbacher B, Peter HH, Eibel H. B-cell activating factor receptor deficiency is associated with an adult-onset antibody deficiency syndrome in humans. Proc Natl Acad Sci U S A. 2009 Aug 18;106(33):13945-50. doi:, 10.1073/pnas.0903543106. Epub 2009 Aug 6. PMID:19666484 doi:10.1073/pnas.0903543106
↑ Yan M, Brady JR, Chan B, Lee WP, Hsu B, Harless S, Cancro M, Grewal IS, Dixit VM. Identification of a novel receptor for B lymphocyte stimulator that is mutated in a mouse strain with severe B cell deficiency. Curr Biol. 2001 Oct 2;11(19):1547-52. PMID:11591325
↑ Kayagaki N, Yan M, Seshasayee D, Wang H, Lee W, French DM, Grewal IS, Cochran AG, Gordon NC, Yin J, Starovasnik MA, Dixit VM. BAFF/BLyS receptor 3 binds the B cell survival factor BAFF ligand through a discrete surface loop and promotes processing of NF-kappaB2. Immunity. 2002 Oct;17(4):515-24. PMID:12387744
↑ 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. Synthetic anti-BR3 antibodies that mimic BAFF binding and target both human and murine B cells. Blood. 2006 Nov 1;108(9):3103-11. Epub 2006 Jul 13. PMID:16840730 doi:10.1182/blood-2006-03-011031

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 See Also
7 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2hfg"

@@ Line 3: / Line 3: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[2hfg]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HFG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2HFG FirstGlance]. <br>
-</td></tr><tr><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><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 Homo sapiens])</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 Homo sapiens])</td></tr>
-<tr><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://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://www.rcsb.org/pdb/explore.do?structureId=2hfg RCSB], [http://www.ebi.ac.uk/pdbsum/2hfg PDBsum]</span></td></tr>
-<table>
+</table>
 == Disease ==
 [[http://www.uniprot.org/uniprot/TR13C_HUMAN TR13C_HUMAN]] Defects in TNFRSF13C are the cause of immunodeficiency common variable type 4 (CVID4) [MIM:[http://omim.org/entry/613494 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.<ref>PMID:19666484</ref>
@@ Line 37: / Line 37: @@
 </StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Hymowitz, S G.]]
+[[Category: Hymowitz, S G]]
 [[Category: Antibody-receptor complex]]
 [[Category: Crd]]

2hfg

From Proteopedia

Revision as of 08:44, 16 January 2015

Crystal structure of hBR3 bound to CB3s-Fab

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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