Analysis of the ligand binding site in Fas (CD95) by site-directed mutagenesis and comparison with TNFR and CD40.

Abstract:

: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.

journal_name

Biochemistry

journal_title

Biochemistry

authors

Starling GC,Kiener PA,Aruffo A,Bajorath J

doi

10.1021/bi972959d

subject

Has Abstract

pub_date

1998-03-17 00:00:00

pages

3723-6

issue

11

eissn

0006-2960

issn

1520-4995

pii

bi972959d

journal_volume

37

pub_type

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