3WD5

Crystal structure of TNFalpha in complex with Adalimumab Fab fragment

Summary for 3WD5

• Entry DOI: 10.2210/pdb3wd5/pdb
• Related: 4G3Y
• Descriptor: Tumor necrosis factor, Adalimumab Light Chain, Adalimumab Heavy Chain, ... (4 entities in total)
• Functional Keywords: antibody binding epitope, immune system
• Biological source: Homo sapiens (human); More
• Cellular location: Cell membrane ; Single-pass type II membrane protein . Tumor necrosis factor, membrane form: Membrane; Single-pass type II membrane protein. Tumor necrosis factor, soluble form: Secreted. C-domain 1: Secreted. C-domain 2: Secreted: P01375
• Total number of polymer chains: 3
• Total formula weight: 63935.43

Authors

Hu, S.,Liang, S.Y.,Guo, Y.J.,Lou, Z.Y. (deposition date: 2013-06-06, release date: 2013-08-14, Last modification date: 2024-10-09)

Primary citation

Hu, S.,Liang, S.Y.,Guo, H.,Zhang, D.,Li, H.,Wang, X.,Yang, W.,Qian, W.,Hou, S.,Wang, H.,Guo, Y.J.,Lou, Z.Y.
Comparison of the inhibition mechanisms of adalimumab and infliximab in treating tumor necrosis factor alpha-associated diseases from a molecular view
J.Biol.Chem., 288:27059-27067, 2013

PubMed Abstract: TNFα-targeting therapy with the use of the drugs Etanercept, Infliximab, and Adalimumab is used in the clinical treatment of various inflammatory and immune diseases. Although all of these reagents function to disrupt the interaction between TNFα and its receptors, clinical investigations showed the advantages of Adalimumab treatment compared with Etanercept and Infliximab. However, the underlying molecular mechanism of action of Adalimumab remains unclear. In our previous work, we presented structural data on how Infliximab binds with the E-F loop of TNFα and functions as a TNFα receptor-binding blocker. To further elucidate the variations between TNFα inhibitors, we solved the crystal structure of TNFα in complex with Adalimumab Fab. The structural observation and the mutagenesis analysis provided direct evidence for identifying the Adalimumab epitope on TNFα and revealed the mechanism of Adalimumab inhibition of TNFα by occupying the TNFα receptor-binding site. The larger antigen-antibody interface in TNFα Adalimumab also provided information at a molecular level for further understanding the clinical advantages of Adalimumab therapy compared with Infliximab.

PubMed: 23943614
DOI: 10.1074/jbc.M113.491530

Experimental method

X-RAY DIFFRACTION (3.101 Å)