Homomeric and heteromeric interactions of the extracellular domains of death receptors and death decoy receptors
Homomeric and heteromeric interactions of the extracellular domains of death receptors and death decoy receptors
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DOI：
10.1016/j.bbrc.2005.03.101
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发表时间：
2005-05-20
影响因子：
3.1
通讯作者：
Kim, YS
中科院分区：
文献类型：
--
作者：
Lee, HW;Lee, SH;Kim, YS
死亡受体(DRs)可以通过与TRAIL的寡聚作用诱导细胞凋亡，而死亡诱骗受体(DCRS)由于缺乏细胞内的功能死亡结构域而不能诱导细胞凋亡。然而，目前尚不清楚DRS和DCRS能否在TRAIL结合之前相互作用形成寡聚复合体。为了解决这个问题，DR4(SDR4)、DR5(SDR5)、DcR1(SDcR1)和DcR2(SDcR2)的胞外结构域(ECD)以可溶的单体形式表达，并通过表面等离子体共振定量它们的结合作用。纯化的SDR和sDcRs呈现天然的二级结构，并与TRAIL结合，结合亲和力在纳摩尔范围内(K-D=类似于10-62 nm)，表明它们具有正确的折叠和功能。除了sDR5不与sDcRs相互作用外，sDR5与sDcRs的微摩尔亲和力相似(K-D=类似于1-9µM)，而sDR5则以同亲和异亲相互作用。我们的结果表明，在没有TRAIL结合的情况下，大多数DRS和DCRS可以通过它们的ECDs横向相互作用形成同质和/或异质复合体。(C)2005 Elsevier Inc.保留所有权利。
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 = similar to 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 = similar to 1-9 mu M), 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. (c) 2005 Elsevier Inc. All rights reserved.