4O4Y

Crystal structure of the anti-hinge rabbit antibody 2095-2 in complex with IDES hinge peptide

Summary for 4O4Y

• Entry DOI: 10.2210/pdb4o4y/pdb
• Related: 4MA3 4O51
• Descriptor: 2095-2 light chain, 2095-2 heavy chain, IDES hinge peptide, ... (5 entities in total)
• Functional Keywords: immunoglobulin fold, antibody, hinge, immune system
• Biological source: Oryctolagus cuniculus, Homo sapiens (rabbit, human); More
• Total number of polymer chains: 3
• Total formula weight: 49154.68

Authors

Malia, T.J.,Teplyakov, A.,Luo, J.,Gilliland, G.L. (deposition date: 2013-12-19, release date: 2014-03-26, Last modification date: 2024-10-30)

Primary citation

Malia, T.J.,Teplyakov, A.,Brezski, R.J.,Luo, J.,Kinder, M.,Sweet, R.W.,Almagro, J.C.,Jordan, R.E.,Gilliland, G.L.
Structure and specificity of an antibody targeting a proteolytically cleaved IgG hinge.
Proteins, 82:1656-1667, 2014

PubMed Abstract: The functional role of human antihinge (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. Proteins 2014; 82:1656-1667. © 2014 Wiley Periodicals, Inc.

PubMed: 24638881
DOI: 10.1002/prot.24545

Experimental method

X-RAY DIFFRACTION (1.85 Å)