Solution structure of the DFF-C domain of DFF45/ICAD. A structural basis for the regulation of apoptotic DNA fragmentation
Solution structure of the DFF-C domain of DFF45/ICAD. A structural basis for the regulation of apoptotic DNA fragmentation
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DOI：
10.1016/s0022-2836(02)00588-0
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发表时间：
2002-08-09
影响因子：
5.6
通讯作者：
Yokoyama, S
中科院分区：
文献类型：
--
作者：
Fukushima, K;Kikuchi, J;Yokoyama, S
DFF 45/ICAD在细胞凋亡的最后阶段具有双重功能，即作为DFF 40/CAD的折叠伴侣和DNA酶抑制剂。在这里，我们提出了解决方案的DFF 45，这是必不可少的伴侣样活性的C-末端结构域的结构。该结构域（DFF-C）的结构由四个α螺旋组成，它们以新颖的螺旋堆积排列折叠。3D结构揭示了DFF-C分子表面上的大簇带负电荷的残基。该观察结果表明，电荷互补在DFF-C与DFF 40的带正电荷的催化结构域的相互作用中起重要作用，并且因此对于DFF 45的伴侣活性起重要作用。DFF-C的结构也为DFF 35（DFF 45的短同种型）中伴侣活性的丧失提供了理论依据。事实上，在DFF 35中，氨基酸序列在构成DFF-C结构的第二个α螺旋的中间被截短，因此疏水核心和负电荷簇都被破坏。(C)2002爱思唯尔科技有限公司。保留所有权利。
DFF45/ICAD has dual functions in the final stage of apoptosis, by acting as both a folding chaperone and a DNase inhibitor of DFF40/CAD. Here, we present the solution structure of the C-terminal domain of DFF45, which is essential for its chaperone-like activity. The structure of this domain (DFF-C) consists of four a helices, which are folded in a novel helix-packing arrangement. The 3D structure reveals a large cluster of negatively charged residues on the molecular surface of DFF-C. This observation suggests that charge complementation plays an important role in the interaction of DFF-C with the positively charged catalytic domain of DFF40, and thus for the chaperone activity of DFF45. The structure of DFF-C also provides a rationale for the loss of the chaperone activity in DFF35, a short isoform of DFF45. Indeed, in DFF35, the amino acid sequence is truncated in the middle of the second alpha helix constituting the structure of DFF-C, and thus both the hydrophobic core and the cluster of negative charges are disrupted. (C) 2002 Elsevier Science Ltd. All rights reserved.