Protein Engineering, Vol. 15, No. 10, 811-815,
October 2002
© 2002 Oxford University Press
Mutation of charged residues in the TR3 death domain does not perturb interaction with TRADD
1 Psychiatry Centre of Excellence for Drug Discovery, 2 Neurology Centre of Excellence for Drug Discovery and 3 Computational, Analytical and Structural Sciences, GlaxoSmithKline, Third Avenue, Harlow, EssexCM19 5AW, UK and 4 Comparative Genomics, GlaxoSmithKline, King of Prussia, PA, USA
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.