title: Asymmetric recruitment of cIAPs by TRAF2.
abstract: Cellular inhibitor of apoptosis protein (cIAP) 1 and cIAP2 set the balance between transcription factor and apoptosis signaling downstream of tumor necrosis factor (TNF) receptor superfamily members by acting as ubiquitin E3 ligases for substrates that are part of the TNF receptor complex. To fulfill this role, cIAPs must be recruited to the receptor complex by TNF-receptor-associated factor (TRAF) 2. In this study, we reconstituted the complex between baculoviral IAP repeat (BIR) 1 of cIAP1 and the coiled-coil region of TRAF2, solved the structure of BIR1 from cIAP1, and mapped key binding residues on each molecule using mutagenesis. Biophysical analysis indicates that a single BIR1 domain binds the trimeric TRAF2 coiled-coil domain. This suggests that only one IAP molecule binds to each TRAF trimer and makes it likely that the dimeric cIAPs crosslink two TRAF trimers.
authors.affiliation: Department of Biochemistry, University of Otago, Dunedin 9054, New Zealand.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Mace
authors.forename: Callum
authors.initials: C
authors.lastname: Smits
authors.forename: David L
authors.initials: DL
authors.lastname: Vaux
authors.forename: John
authors.initials: J
authors.lastname: Silke
authors.forename: Catherine L
authors.initials: CL
authors.lastname: Day
mesh_terms: D000595:Amino Acid Sequence; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D002942:Circular Dichroism; D018360:Crystallography, X-Ray; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D047992:TNF Receptor-Associated Factor 2 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases
chemical_list: D051034:Inhibitor of Apoptosis Proteins; D047992:TNF Receptor-Associated Factor 2; C494832:BIRC3 protein, human; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D044767:Ubiquitin-Protein Ligases