2hfg
From Proteopedia
(New page: 200px<br /> <applet load="2hfg" size="450" color="white" frame="true" align="right" spinBox="true" caption="2hfg, resolution 2.61Å" /> '''Crystal structure o...) |
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| - | [[Image:2hfg.gif|left|200px]]<br /> | + | [[Image:2hfg.gif|left|200px]]<br /><applet load="2hfg" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2hfg" size=" | + | |
caption="2hfg, resolution 2.61Å" /> | caption="2hfg, resolution 2.61Å" /> | ||
'''Crystal structure of hBR3 bound to CB3s-Fab'''<br /> | '''Crystal structure of hBR3 bound to CB3s-Fab'''<br /> | ||
==Overview== | ==Overview== | ||
| - | BR3, which is expressed on all mature B cells, is a specific receptor for | + | 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. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2HFG is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | + | 2HFG is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences 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]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Hymowitz, S | + | [[Category: Hymowitz, S G.]] |
[[Category: antibody-receptor complex]] | [[Category: antibody-receptor complex]] | ||
[[Category: crd]] | [[Category: crd]] | ||
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[[Category: tnfrsf]] | [[Category: tnfrsf]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:41:17 2008'' |
Revision as of 15:41, 21 February 2008
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Crystal structure of hBR3 bound to CB3s-Fab
Contents |
Overview
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.
Disease
Known disease associated with this structure: Kappa light chain deficiency OMIM:[147200]
About this Structure
2HFG is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
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
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