Sandbox8: Difference between revisions
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Name: Marissa McGarry 03/02/09 | Name: Marissa McGarry 03/02/09 | ||
The overall structure of TRAIL is a set of 13 <scene name='Sandbox8/Overall_structure/1'>beta sheets</scene>. | The overall structure of TRAIL is a set of 13 <scene name='Sandbox8/Overall_structure/1'>beta sheets</scene> | ||
<scene name='Sandbox8/Hydophobic_element/1'>Phe181</scene> is a hydrophobic element on the surface of the protein. | |||
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. | 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. | ||