2hff: Difference between revisions

Revision as of 18:41, 21 February 2008

Crystal structure of CB2 Fab

OverviewOverview

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.

About this StructureAbout this Structure

2HFF is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

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

Page seeded by OCA on Thu Feb 21 17:41:15 2008

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OCA

@@ Line 4: / Line 4: @@
 ==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.
+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.
 ==About this Structure==
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 [[Category: Homo sapiens]]
 [[Category: Protein complex]]
-[[Category: Hymowitz, S.G.]]
+[[Category: Hymowitz, S G.]]
 [[Category: combinatorial selection]]
 [[Category: fab fragment]]
 [[Category: phage libraries]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jan 29 20:19:57 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:41:15 2008''