title: Mutation of charged residues in the TR3 death domain does not perturb interaction with TRADD.
abstract: 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.
authors.affiliation: Psychiatry Centre of Excellence for Drug Discovery, GlaxoSmithKline, Third Avenue, Harlow, EssexCM19 5AW, UK.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Tunbridge
authors.forename: Colin
authors.initials: C
authors.lastname: Dingwall
authors.forename: Colin
authors.initials: C
authors.lastname: Edge
authors.forename: Madhavi
authors.initials: M
authors.lastname: Konduri
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: DeMarini
authors.forename: George P
authors.initials: GP
authors.lastname: Livi
authors.forename: Peter R
authors.initials: PR
authors.lastname: Maycox
mesh_terms: D000409:Alanine / Q000235:genetics; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D024342:Amino Acids, Acidic / Q000235:genetics; D024361:Amino Acids, Basic / Q000235:genetics; D000818:Animals; D017931:DNA Primers / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011233:Precipitin Tests; D017434:Protein Structure, Tertiary / Q000235:genetics; D011506:Proteins / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics* / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D012997:Solvents / Q000737:chemistry; D047990:TNF Receptor-Associated Factor 1; D020798:Two-Hybrid System Techniques
chemical_list: D024342:Amino Acids, Acidic; D024361:Amino Acids, Basic; D017931:DNA Primers; D011506:Proteins; D018124:Receptors, Tumor Necrosis Factor; D012997:Solvents; D047990:TNF Receptor-Associated Factor 1; D000409:Alanine