title: Homomeric and heteromeric interactions of the extracellular domains of death receptors and death decoy receptors.
abstract: Death receptors (DRs) can induce apoptosis by oligomerization with TRAIL, whereas death decoy receptors (DcRs) cannot, due to their lack of functional intracellular death domains. However, it is not known whether DRs and DcRs can interact with one another to form oligomeric complexes prior to TRAIL binding. To address this issue, the extracellular domains (ECDs) of DR4 (sDR4), DR5 (sDR5), DcR1 (sDcR1), and DcR2 (sDcR2) were expressed in a soluble, monomeric form, and their binding interactions were quantified by surface plasmon resonance. The purified sDRs and sDcRs exhibited native-like secondary structure and bound to TRAIL with binding affinities in the nanomolar range (K(D)= approximately 10-62 nM), suggesting that they were properly folded and functional. The soluble receptors interacted homophilically and heterophilically with similar micromolar range affinities (K(D)= approximately 1-9 microM), with the exception that sDR5 did not interact with the sDcRs. Our results suggest that most DRs and DcRs can laterally interact through their ECDs to form homomeric and/or heteromeric complexes in the absence of TRAIL binding.
authors.affiliation: Department of Molecular Science and Technology, Ajou University, Yeongtong-gu, Suwon 443-749, Republic of Korea.
authors.forename: Hyun-Wook
authors.initials: HW
authors.lastname: Lee
authors.forename: Seung-Hyun
authors.initials: SH
authors.lastname: Lee
authors.forename: Hae-Won
authors.initials: HW
authors.lastname: Lee
authors.forename: Yeon-Woo
authors.initials: YW
authors.lastname: Ryu
authors.forename: Myung-Hee
authors.initials: MH
authors.lastname: Kwon
authors.forename: Yong-Sung
authors.initials: YS
authors.lastname: Kim
mesh_terms: D051017:Apoptosis Regulatory Proteins; D019281:Dimerization; D045604:Extracellular Fluid / Q000737:chemistry; D006801:Humans; D019169:Jurkat Cells; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D017510:Protein Folding; D017433:Protein Structure, Secondary; D018124:Receptors, Tumor Necrosis Factor / Q000737:chemistry* / Q000378:metabolism; D020349:Surface Plasmon Resonance; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000737:chemistry* / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D008562:Membrane Glycoproteins; D018124:Receptors, Tumor Necrosis Factor; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha