TY - JOUR
T1 - Homomeric and heteromeric interactions of the extracellular domains of death receptors and death decoy receptors
AU - Lee, Hyun Wook
AU - Lee, Seung Hyun
AU - Lee, Hae Won
AU - Ryu, Yeon Woo
AU - Kwon, Myung Hee
AU - Kim, Yong Sung
N1 - Funding Information:
We thank Prof. D.W. Seol (University of Pittsburgh) for the gift of pETdwTRAIL, Prof. Schneider (Universite De Lausanne) for ps404hTRAILR2-Fc, Prof. Y.H. Lee (Yonsei University) for DR4-pCR3, and Prof. C. Vincenz (U. of Michigan) for pCMV1FLAGTRID and pCMV1FLAGTRIL. We also thank Prof. Kyung-Sook Choi (Ajou University) for providing the apoptosis assay, Woo-Ram Lee and Yun-Sun Jang for excellent technical assistance with protein purifications, and Profs. Do-Hyun Jo (Ajou University) and Kyung-Kyu Kim (SungKyunKwan University) for use of their FPLC system and Jasco CD spectrometer, respectively. This work was supported by a Korea Research Foundation Grant funded by the Korean Government to Y.-S.K. (R08-2004-000-10077-0).
PY - 2005/5/20
Y1 - 2005/5/20
N2 - 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 = ∼10-62 nM), suggesting that they were properly folded and functional. The soluble receptors interacted homophilically and heterophilically with similar micromolar range affinities (KD = ∼1-9 μM), 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.
AB - 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 = ∼10-62 nM), suggesting that they were properly folded and functional. The soluble receptors interacted homophilically and heterophilically with similar micromolar range affinities (KD = ∼1-9 μM), 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.
UR - https://www.scopus.com/pages/publications/17044382532
UR - https://www.scopus.com/pages/publications/17044382532#tab=citedBy
U2 - 10.1016/j.bbrc.2005.03.101
DO - 10.1016/j.bbrc.2005.03.101
M3 - Article
C2 - 15823571
AN - SCOPUS:17044382532
SN - 0006-291X
VL - 330
SP - 1205
EP - 1212
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 4
ER -