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Analysis of the ligand binding site in Fas (CD95) by site-directed mutagenesis and comparison with TNFR and CD40.
Starling, G C; Kiener, P A; Aruffo, A; Bajorath, J.
Afiliación
  • Starling GC; Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, Washington 98121, USA. starling@bms.com
Biochemistry ; 37(11): 3723-6, 1998 Mar 17.
Article en En | MEDLINE | ID: mdl-9521690
Fas and its ligand (FasL) are members of the tumor necrosis factor receptor (TNFR) and tumor necrosis factor (TNF) superfamilies, respectively. Fas-FasL interactions trigger controlled cell death (apoptosis) in the immune system and thus play a key role in the regulation of immune responses. Structural details of the Fas-Fas ligand interaction are currently unknown. Previously, six Fas residues were identified by mutagenesis as important for ligand binding. We have now extended our mutagenesis analysis and identified additional residues which contribute to the Fas-FasL interaction. Candidate and control residues were selected based on a molecular model of the Fas extracellular region. Although residues in all three extracellular domains were identified to contribute to binding, the Fas-FasL interaction is centered on the second TNFR-like domain. Important residues were compared to critical positions in TNFR and CD40, another member of the TNFR family.
Asunto(s)
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Glicoproteínas de Membrana / Mutagénesis Sitio-Dirigida / Receptores del Factor de Necrosis Tumoral / Receptor fas / Antígenos CD40 Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Biochemistry Año: 1998 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Glicoproteínas de Membrana / Mutagénesis Sitio-Dirigida / Receptores del Factor de Necrosis Tumoral / Receptor fas / Antígenos CD40 Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Biochemistry Año: 1998 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos