3X3F

TRAIL-R2 Extracellular Region Complexed to a Fab fragment from Human Agonist Antibody KMTR2

Summary for 3X3F

• Entry DOI: 10.2210/pdb3x3f/pdb
• Related: 3X3G
• Descriptor: Heavy chain of KMTR2, Light chain of KMTR2, Tumor necrosis factor receptor superfamily member 10B, ... (7 entities in total)
• Functional Keywords: trail-r2, agonist antibody, apoptosis-immune system complex, apoptosis/immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 3
• Total formula weight: 64943.57

Authors

Tamada, T. (deposition date: 2015-01-20, release date: 2015-12-23, Last modification date: 2024-10-30)

Primary citation

Tamada, T.,Shinmi, D.,Ikeda, M.,Yonezawa, Y.,Kataoka, S.,Kuroki, R.,Mori, E.,Motoki, K.
TRAIL-R2 Superoligomerization Induced by Human Monoclonal Agonistic Antibody KMTR2
Sci Rep, 5:17936-17936, 2015

PubMed Abstract: The fully human monoclonal antibody KMTR2 acts as a strong direct agonist for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor 2 (TRAIL-R2), which is capable of inducing apoptotic cell death without cross-linking. To investigate the mechanism of direct agonistic activity induced by KMTR2, the crystal structure of the extracellular region of TRAIL-R2 and a Fab fragment derived from KMTR2 (KMTR2-Fab) was determined to 2.1 Å resolution. Two KMTR2-Fabs assembled with the complementarity-determining region 2 of the light chain via two-fold crystallographic symmetry, suggesting that the KMTR2-Fab assembly tended to enhance TRAIL-R2 oligomerization. A single mutation at Asn53 to Arg located at the two-fold interface in the KMTR2 resulted in a loss of its apoptotic activity, although it retained its antigen-binding activity. These results indicate that the strong agonistic activity, such as apoptotic signaling and tumor regression, induced by KMTR2 is attributed to TRAIL-R2 superoligomerization induced by the interdimerization of KMTR2.

PubMed: 26672965
DOI: 10.1038/srep17936

Experimental method

X-RAY DIFFRACTION (2.1 Å)