Homomeric and heteromeric interactions of the extracellular domains of death receptors and death decoy receptors

Hyun Wook Lee; Seung Hyun Lee; Hae Won Lee; Yeon Woo Ryu; Myung Hee Kwon; Yong Sung Kim

doi:10.1016/j.bbrc.2005.03.101

Homomeric and heteromeric interactions of the extracellular domains of death receptors and death decoy receptors

Hyun Wook Lee
, Seung Hyun Lee
, Hae Won Lee
, Yeon Woo Ryu
, Myung Hee Kwon
, Yong Sung Kim

Research output: Contribution to journal › Article › peer-review

57 Scopus citations

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 = ∼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 = ∼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.

Original language	English (US)
Pages (from-to)	1205-1212
Number of pages	8
Journal	Biochemical and Biophysical Research Communications
Volume	330
Issue number	4
DOIs	https://doi.org/10.1016/j.bbrc.2005.03.101
State	Published - May 20 2005
Externally published	Yes

Bibliographical note

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).

Keywords

Death decoy receptors
Death receptors
Homomeric and heteromeric interactions
SPR
TRAIL

Publisher link

10.1016/j.bbrc.2005.03.101

Find It

Find It at U of M Libraries

Cite this

@article{cc4007c8b7d94f189d3f0cd9704271cd,

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 = ∼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.",

keywords = "Death decoy receptors, Death receptors, Homomeric and heteromeric interactions, SPR, TRAIL",

author = "Lee, \{Hyun Wook\} and Lee, \{Seung Hyun\} and Lee, \{Hae Won\} and Ryu, \{Yeon Woo\} and Kwon, \{Myung Hee\} and Kim, \{Yong Sung\}",

note = "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).",

year = "2005",

month = may,

day = "20",

doi = "10.1016/j.bbrc.2005.03.101",

language = "English (US)",

volume = "330",

pages = "1205--1212",

journal = "Biochemical and Biophysical Research Communications",

issn = "0006-291X",

publisher = "Elsevier B.V.",

number = "4",

}

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.

KW - Death decoy receptors

KW - Death receptors

KW - Homomeric and heteromeric interactions

KW - SPR

KW - TRAIL

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 -

Homomeric and heteromeric interactions of the extracellular domains of death receptors and death decoy receptors

Abstract

Bibliographical note

Keywords

Publisher link

Find It

Other files and links

Fingerprint

Cite this