3SKJ

Structural And Functional Characterization of an Agonistic Anti-Human EphA2 Monoclonal Antibody

Summary for 3SKJ

• Entry DOI: 10.2210/pdb3skj/pdb
• Descriptor: Antibody, light chain, Antibody, heavy chain, Ephrin type-A receptor 2, ... (4 entities in total)
• Functional Keywords: fab, receptor, ig fold, ephrin receptor, antibody, antigen, extra-cellular, immune system
• Biological source: Homo sapiens (human); More
• Cellular location: Cell membrane ; Single- pass type I membrane protein : P29317
• Total number of polymer chains: 6
• Total formula weight: 142941.75

Authors

Oganesyan, V.Y.,Wu, H.,Dall'Acqua, W.F. (deposition date: 2011-06-22, release date: 2011-08-31, Last modification date: 2024-11-27)

Primary citation

Peng, L.,Oganesyan, V.,Damschroder, M.M.,Wu, H.,Dall'Acqua, W.F.
Structural and functional characterization of an agonistic anti-human EphA2 monoclonal antibody.
J.Mol.Biol., 413:390-405, 2011

PubMed Abstract: We report here the three-dimensional structure of human ephrin type A receptor 2 (EphA2) bound to the Fab (fragment antigen binding) of an agonistic human antibody (1C1; IgG1/κ). The structure of the corresponding complex was solved at a resolution of 2.5 Å using molecular replacement and constitutes the first reported structure of a human ephrin receptor bound to an antibody. We have also defined the corresponding functional epitope using a mutagenesis-based approach. This study revealed discrete structural features that determine the fine specificity of 1C1 to EphA2. Our data also provided a molecular basis for 1C1 mechanism of action. More precisely, we propose that its agonistic, internalizing properties are the result of ligand mimicry by the third heavy-chain complementarity-determining region of 1C1. Because EphA2 is an important contributor to cancer formation and progression, these findings may have implications for designing the next generation of anti-tumor therapies.

PubMed: 21867711
DOI: 10.1016/j.jmb.2011.08.018

Experimental method

X-RAY DIFFRACTION (2.5 Å)