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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
30
|
| pubmed:dateCreated |
1997-9-9
|
| pubmed:abstractText |
The death-inducing receptor Fas is activated when cross-linked by the type II membrane protein Fas ligand (FasL). When human soluble FasL (sFasL, containing the extracellular portion) was expressed in human embryo kidney 293 cells, the three N-linked glycans of each FasL monomer were found to be essential for efficient secretion. Based on the structure of the closely related lymphotoxin alpha-tumor necrosis factor receptor I complex, a molecular model of the FasL homotrimer bound to three Fas molecules was generated using knowledge-based protein modeling methods. Point mutations of amino acid residues predicted to affect the receptor-ligand interaction were introduced at three sites. The F275L mutant, mimicking the loss of function murine gld mutation, exhibited a high propensity for aggregation and was unable to bind to Fas. Mutants P206R, P206D, and P206F displayed reduced cytotoxicity toward Fas-positive cells with a concomitant decrease in the binding affinity for the recombinant Fas-immunoglobulin Fc fusion proteins. Although the cytotoxic activity of mutant Y218D was unaltered, mutant Y218R was inactive, correlating with the prediction that Tyr-218 of FasL interacts with a cluster of three basic amino acid side chains of Fas. Interestingly, mutant Y218F could induce apoptosis in murine, but not human cells.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD95,
http://linkedlifedata.com/resource/pubmed/chemical/FASLG protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Fas Ligand Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Fasl protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Ligands,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proline,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrosine
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jul
|
| pubmed:issn |
0021-9258
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
25
|
| pubmed:volume |
272
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
18827-33
|
| pubmed:dateRevised |
2006-11-15
|
| pubmed:meshHeading |
pubmed-meshheading:9228058-Amino Acid Sequence,
pubmed-meshheading:9228058-Animals,
pubmed-meshheading:9228058-Antigens, CD95,
pubmed-meshheading:9228058-Binding Sites,
pubmed-meshheading:9228058-Chromatography, Gel,
pubmed-meshheading:9228058-Enzyme-Linked Immunosorbent Assay,
pubmed-meshheading:9228058-Fas Ligand Protein,
pubmed-meshheading:9228058-Glycosylation,
pubmed-meshheading:9228058-Humans,
pubmed-meshheading:9228058-Jurkat Cells,
pubmed-meshheading:9228058-Ligands,
pubmed-meshheading:9228058-Membrane Glycoproteins,
pubmed-meshheading:9228058-Mice,
pubmed-meshheading:9228058-Models, Molecular,
pubmed-meshheading:9228058-Molecular Sequence Data,
pubmed-meshheading:9228058-Mutagenesis,
pubmed-meshheading:9228058-Proline,
pubmed-meshheading:9228058-Sequence Alignment,
pubmed-meshheading:9228058-Solubility,
pubmed-meshheading:9228058-Species Specificity,
pubmed-meshheading:9228058-Tyrosine
|
| pubmed:year |
1997
|
| pubmed:articleTitle |
Characterization of Fas (Apo-1, CD95)-Fas ligand interaction.
|
| pubmed:affiliation |
Institute of Biochemistry, University of Lausanne, BIL Biomedical Research Center, CH-1066 Epalinges, Switzerland. pascal.schneider@ib.unil.ch
|
| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|