Key result
Mutation of charged residues in the second and third helices of the TR3 death domain failed to perturb self-interaction or interaction with TRADD.
The interaction between the TR3 death domain and TRADD differs from that of TNFR1, as mutations in charged residues of TR3's second and third helices do not disrupt the interaction.
TR3-TRADD binding differs from TNFR1; leaves open distinct death-domain interfaces and requires validation beyond animal models.
Members of the death receptor family play a prominent role in developmental and pathological neuronal cell death. The death signal is transduced via interaction between the death domain of the receptor and an intracellular adapter, TRADD. We performed alanine-scanning mutagenesis of specific charged residues in the TR3 death domain to determine whether they play a crucial role in TR3-TR3 and TR3-TRADD interaction. Mutation of charged residues in the second and third helices of the TR3 death domain failed to perturb self-interaction or interaction with TRADD. These data suggest that despite some similarity between the death domains of TR3 and TNFR1 the nature of the interaction with TRADD differs from that reported for TNFR1.
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Dingwall et al. (2002) studied this question. Alanine-scanning mutagenesis of specific charged residues in the TR3 death domain was evaluated on TR3-TR3 and TR3-TRADD interaction. Mutation of charged residues in the second and third helices of the TR3 death domain failed to perturb self-interaction or interaction with TRADD.
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