4ma3

Crystal structure of anti-hinge rabbit antibody C2095

spinqualitylabelsall models 4ma3, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4ma3 is a 4 chain structure with sequence from European rabbit. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ACT, SO4 NonStd Res: PCA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed The functional role of human anti-hinge (HAH) autoantibodies in normal health and disease remains elusive, but recent evidence supports their role in the host response to IgG cleavage by proteases that are prevalent in certain disorders. Characterization and potential exploitation of these HAH antibodies has been hindered by the absence of monoclonal reagents. 2095-2 is a rabbit monoclonal antibody targeting the IdeS-cleaved hinge of human IgG1. We have determined the crystal structure of the Fab of 2095-2 and its complex with a hinge analog peptide. The antibody is selective for the C-terminally cleaved hinge ending in G236 and this interaction involves an uncommon disulfide in VL CDR3. We probed the importance of the disulfide in VL CDR3 through engineering variants. We identified one variant, QAA, which does not require the disulfide for biological activity or peptide binding. The structure of this variant offers a starting point for further engineering of 2095-2 with the same specificity, but lacking the potential manufacturing liability of an additional disulfide. (c) Proteins 2014;. (c) 2014 Wiley Periodicals, Inc. Structure and specificity of an antibody targeting a proteolytically-cleaved IgG hinge.,Malia TJ, Teplyakov A, Brezski RJ, Luo J, Kinder M, Sweet RW, Almagro JC, Jordan RE, Gilliland GL Proteins. 2014 Mar 17. doi: 10.1002/prot.24545. PMID:24638881 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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