2hff

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[[Image:2hff.gif|left|200px]]
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{{STRUCTURE_2hff| PDB=2hff | SCENE= }}
{{STRUCTURE_2hff| PDB=2hff | SCENE= }}
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'''Crystal structure of CB2 Fab'''
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===Crystal structure of CB2 Fab===
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==Overview==
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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.
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The line below this paragraph, {{ABSTRACT_PUBMED_16840730}}, adds the Publication Abstract to the page
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(as it appears on PubMed at http://www.pubmed.gov), where 16840730 is the PubMed ID number.
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{{ABSTRACT_PUBMED_16840730}}
==About this Structure==
==About this Structure==
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[[Category: Fab fragment]]
[[Category: Fab fragment]]
[[Category: Phage library]]
[[Category: Phage library]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 06:13:41 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 02:48:35 2008''

Revision as of 23:48, 27 July 2008

Image:2hff.png

Template:STRUCTURE 2hff

Crystal structure of CB2 Fab

Template:ABSTRACT PUBMED 16840730

About this Structure

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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