6fxn | pdb_00006fxn

Crystal structure of human BAFF in complex with Fab fragment of anti-BAFF antibody belimumab

spinqualitylabelsall models 6fxn, resolution 2.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6fxn is a 18 chain structure. This structure supersedes the now removed PDB entry 6erx. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [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. Isoform 2 seems to inhibit isoform 1 secretion and bioactivity (By similarity). 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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