Proc Natl Acad Sci U S A. 1999 Apr 13;96(8):4552-7.

Defective CD95/APO-1/Fas signal complex formation in the human autoimmune lymphoproliferative syndrome, type Ia.External

Martin, D. A., Zheng, L., Siegel, R. M., Huang, B., Fisher, G. H., Wang, J., Jackson, C. E., Puck, J. M., Dale, J., Straus, S. E., Peter, M. E., Krammer, P. H., Fesik, S., Lenardo, M. J.,
--- - Laboratory of Immunology, National Institutes of Health, Bethesda, MD 20892, USA.
Heterozygous mutations in the CD95 (APO-1/Fas) receptor occur in most individuals with autoimmune lymphoproliferative syndrome (ALPS) and dominantly interfere with apoptosis by an unknown mechanism. We show that local or global alterations in the structure of the cytoplasmic death domain from nine independent ALPS CD95 death-domain mutations result in a failure to bind the FADD/MORT1 signaling protein. Despite heterozygosity for the abnormal allele, lymphocytes from ALPS patients showed markedly decreased FADD association and a loss of caspase recruitment and activation after CD95 crosslinking. These data suggest that intracytoplasmic CD95 mutations in ALPS impair apoptosis chiefly by disrupting death-domain interactions with the signaling protein FADD/MORT1.
PMID: 10200300External
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
In vitro interaction
  DD1 DD2 Reference
Family DD1 DD2 Method Species Region Expression Species Region Expression
DD FADD Link Fas GST fusion protein pull-down Not specified Not specified In vitro translation Human 174-319 E.coli 10200300
(Link: click this icon to show interactions only between the two corresponding DDs)
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
In vivo interaction
  Endogenous
expression
Overexpression DD1 DD2 Reference
Family DD1 DD2 Method Species Region Species Region
DD FADD Link Fas Co-immunoprecipitation HEK293 Not used Human 174-319 10200300
(Link: click this icon to show interactions only between the two corresponding DDs)
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
Characterization
  Stoichiometry Affinity Protein-Protein interface Reference
Family DD1 DD2 Method Mutation Complex structure
DD FADD Link Fas Co-immunoprecipitation V238N, D244V, Q257X, A241D, I294S (Fas) 10200300
DD FADD Link Fas GST fusion protein pull-down T225P, Q257X, A241D, I294S, D244V, R234Q, L278X, R234P, Q260X, I238N (Fas) 10200300
(Link: click this icon to show interactions only between the two corresponding DDs)