2.8 A resolution crystal structure of human TRAIL, a cytokine with selective antitumor activity.
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.
Cha
S S
SS
Department of Life Science and School of Environmental Engineering, Pohang University of Science and Technology, Kyungbuk, Korea.
Kim
M S
MS
Choi
Y H
YH
Sung
B J
BJ
Shin
N K
NK
Shin
H C
HC
Sung
Y C
YC
Oh
B H
BH
D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins; D001665:Binding Sites; D003461:Crystallography; D006801:Humans; D008233:Lymphotoxin-alpha / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I; D013329:Structure-Activity Relationship; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000737:chemistry* / Q000378:metabolism
D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; D008233:Lymphotoxin-alpha; D008562:Membrane Glycoproteins; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D053221:TNF-Related Apoptosis-Inducing Ligand; C105190:TNFRSF10A protein, human; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha