Dataset Information

TRAIL-R2 Superoligomerization Induced by Human Monoclonal Agonistic Antibody KMTR2.

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.

SUBMITTER: Tamada T

PROVIDER: S-EPMC4682084 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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TRAIL-R2 Superoligomerization Induced by Human Monoclonal Agonistic Antibody KMTR2.

Tamada Taro T Shinmi Daisuke D Ikeda Masahiro M Yonezawa Yasushi Y Kataoka Shiro S Kuroki Ryota R Mori Eiji E Motoki Kazuhiro K

Scientific reports 20151217

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 comp ...[more]

PMID: 26672965

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Dataset Information

TRAIL-R2 Superoligomerization Induced by Human Monoclonal Agonistic Antibody KMTR2.

Publications

TRAIL-R2 Superoligomerization Induced by Human Monoclonal Agonistic Antibody KMTR2.

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