View source for 6fxn


==Crystal structure of human BAFF in complex with Fab fragment of anti-BAFF antibody belimumab==
<StructureSection load='6fxn' size='340' side='right' caption='[[6fxn]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6fxn]] is a 18 chain structure. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=6erx 6erx]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FXN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FXN FirstGlance]. <br>
</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=6fxn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fxn OCA], [http://pdbe.org/6fxn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6fxn RCSB], [http://www.ebi.ac.uk/pdbsum/6fxn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6fxn ProSAT]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/TN13B_HUMAN TN13B_HUMAN]] Cytokine that binds to TNFRSF13B/TACI and TNFRSF17/BCMA. TNFSF13/APRIL binds to the same 2 receptors. Together, they form a 2 ligands -2 receptors pathway involved in the stimulation of B- and T-cell function and the regulation of humoral immunity. A third B-cell specific BAFF-receptor (BAFFR/BR3) promotes the survival of mature B-cells and the B-cell response.<ref>PMID:10973284</ref>   Isoform 2 seems to inhibit isoform 1 secretion and bioactivity (By similarity).<ref>PMID:10973284</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The B cell survival factor (TNFSF13B/BAFF) is often elevated in autoimmune diseases and is targeted in the clinic for the treatment of systemic lupus erythematosus. BAFF contains a loop region designated the flap, which is dispensable for receptor binding. Here we show that the flap of BAFF has two functions. In addition to facilitating the formation of a highly active BAFF 60-mer as shown previously, it also converts binding of BAFF to TNFRSF13C (BAFFR) into a signaling event via oligomerization of individual BAFF-BAFFR complexes. Binding and activation of BAFFR can therefore be targeted independently to inhibit or activate the function of BAFF. Moreover, structural analyses suggest that the flap of BAFF 60-mer temporarily prevents binding of an anti-BAFF antibody (belimumab) but not of a decoy receptor (atacicept). The observed differences in profiles of BAFF inhibition may confer distinct biological and clinical efficacies to these therapeutically relevant inhibitors.

A loop region of BAFF controls B cell survival and regulates recognition by different inhibitors.,Vigolo M, Chambers MG, Willen L, Chevalley D, Maskos K, Lammens A, Tardivel A, Das D, Kowalczyk-Quintas C, Schuepbach-Mallepell S, Smulski CR, Eslami M, Rolink A, Hummler E, Samy E, Fomekong Nanfack Y, Mackay F, Liao M, Hess H, Jiang X, Schneider P Nat Commun. 2018 Mar 23;9(1):1199. doi: 10.1038/s41467-018-03323-8. PMID:29572442<ref>PMID:29572442</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6fxn" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Jiang, X]]
[[Category: Lammens, A]]
[[Category: Maskos, K]]
[[Category: Schneider, P]]
[[Category: Willen, L]]
[[Category: Antibody]]
[[Category: B cell]]
[[Category: Baff]]
[[Category: Cytokine]]
[[Category: Immune system]]
[[Category: Immunology]]
[[Category: Protero]]