Abstract
TRAIL is a newly identified cytokine belonging to the large tumor necrosis factor (TNF) family. TRAIL is a novel molecule inducing apoptosis in a wide variety of tumor cells but not in normal cells. To help in elucidating its biological roles and designing mutants with improved therapeutic potential, we have determined the crystal structure of human TRAIL. The structure reveals that a unique frame insertion of 12-16 amino acids adopts a salient loop structure penetrating into the receptor-binding site. The loop drastically alters the common receptor-binding surface of the TNF family most likely for the specific recognition of cognate partners. A structure-based mutagenesis study demonstrates a critical role of the insertion loop in the cytotoxic activity of TRAIL.
| Original language | English |
|---|---|
| Pages (from-to) | 253-261 |
| Number of pages | 9 |
| Journal | Immunity |
| Volume | 11 |
| Issue number | 2 |
| DOIs | |
| State | Published - Aug 1999 |
Bibliographical note
Funding Information:We thank H.-S. Shin for critical review of the manuscript and J.-W. Jung and J. Park for help in preparing the figures. This study made use of the x-ray facility at Pohang Light Source and beamline 18B at Photon Factory, Japan, and was supported by The Molecular Medicine Research Group Program of the Ministry of Science and Technology and in part by the grant from the Immunomodulation Research Center, University of Ulsan.
