Cysteine 230 is essential for the structure and activity of the cytotoxic ligand TRAIL.

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Serval ID
serval:BIB_15C09F6E6B8D
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Cysteine 230 is essential for the structure and activity of the cytotoxic ligand TRAIL.
Journal
Journal of Biological Chemistry
Author(s)
Bodmer J.L., Meier P., Tschopp J., Schneider P.
ISSN
0021-9258 (Print)
ISSN-L
0021-9258
Publication state
Published
Issued date
2000
Volume
275
Number
27
Pages
20632-20637
Language
english
Abstract
Unlike other tumor necrosis factor family members, the cytotoxic ligand tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)/Apo-2L contains an unpaired cysteine residue (Cys(230)) in its receptor-binding domain. Here we show that the biological activity of both soluble recombinant TRAIL and cell-associated, full-length TRAIL is critically dependent on the presence of Cys(230). Mutation of Cys(230) to alanine or serine strongly affected its ability to kill target cells. Binding to its receptors was decreased by at least 200-fold, and the stability of its trimeric structure was reduced. In recombinant TRAIL, Cys(230) was found engaged either in interchain disulfide bridge formation, resulting in poorly active TRAIL, or in the chelation of one zinc atom per TRAIL trimer in the active, pro-apoptotic form of TRAIL.
Keywords
Amino Acid Sequence, Apoptosis, Apoptosis Regulatory Proteins, Binding Sites, Cysteine/chemistry, Disulfides/chemistry, Humans, Hydrogen-Ion Concentration, Membrane Glycoproteins/chemistry, Membrane Glycoproteins/genetics, Molecular Sequence Data, Mutation, Protein Conformation, Receptors, Tumor Necrosis Factor/metabolism, Recombinant Proteins/chemistry, Recombinant Proteins/metabolism, Sequence Alignment, TNF-Related Apoptosis-Inducing Ligand, Tumor Cells, Cultured, Tumor Necrosis Factor-alpha/chemistry, Tumor Necrosis Factor-alpha/genetics, Zinc/chemistry
Pubmed
Web of science
Open Access
Yes
Create date
24/01/2008 15:18
Last modification date
20/08/2019 12:44
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