ZBP1 subcellular localization and association with stress granules is controlled by its Z-DNA binding domains.
ZBP1 subcellular localization and association with stress granules is controlled by its Z-DNA binding domains.
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DOI：
10.1093/nar/gkl575
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发表时间：
2006
影响因子：
14.9
通讯作者：
Rothenburg, Stefan
中科院分区：
文献类型：
--
作者：
Deigendesch, Nikolaus;Koch-Nolte, Friedrich;Rothenburg, Stefan
Z-DNA结合蛋白1是一个含有Z-α结构域的蛋白质家族，它能与左手Z-DNA和Z-RNA特异结合。与Zα家族中的所有脊椎动物蛋白一样，它含有两个Zα样结构域，并且高度受免疫刺激的诱导。圆二色谱和电泳迁移率分析表明，两个ZDNA结构域都可以独立地与Z-α结合，并且当两个结构域连接时，底物结合能力大大增强。全长ZBP1和一个缺少第一个Zα结构域的显著剪接变体(ΔZα)显示出明显不同的亚细胞定位。ZBP1ΔZα全长蛋白呈细小点状分布在胞浆内，胞质颗粒较大。第一个Zα结构域中与Z-DNA结合重要的残基的突变导致了与ZBP1ΔZα相似的分布。ZBP1ΔZα颗粒不同于应力颗粒和加工体，但与它们动态地相互作用。多聚体的稳定导致ZBP1mRNA ZΔ颗粒的解体，表明α是完整的组成部分。热休克和亚砷酸盐暴露对ZBP_1亚型有相反的影响：当ZBP_1ΔZ_α颗粒解体时，ZBP_1全长积累在SGS中。我们的数据将ZBP1与mRNA分选和代谢联系起来，并表明了ZBP1亚型的不同作用。
Z-DNA binding protein 1 (ZBP1) belongs to a family of proteins that contain the Zα domain, which binds specifically to left-handed Z-DNA and Z-RNA. Like all vertebrate proteins in the Zα family, it contains two Zα-like domains and is highly inducible by immunostimulation. Using circular dichroism spectroscopy and electrophoretic mobility shift assays we show that both Zα domains can bind Z-DNA independently and that substrate binding is greatly enhanced when both domains are linked. Full length ZBP1 and a prominent splice variant lacking the first Zα domain (ΔZα) showed strikingly different subcellular localizations. While the full length protein showed a finely punctate cytoplasmatic distribution, ZBP1ΔZα accumulated in large cytoplasmic granules. Mutation of residues important for Z-DNA binding in the first Zα domain resulted in a distribution comparable to that of ZBP1ΔZα. The ZBP1ΔZα granules are distinct from stress granules (SGs) and processing bodies but dynamically interacted with these. Polysome stabilization led to the disassembly of ZBP1ΔZα granules, indicating that mRNA are integral components. Heat shock and arsenite exposure had opposing effects on ZBP1 isoforms: while ZBP1ΔZα granules disassembled, full length ZBP1 accumulated in SGs. Our data link ZBP1 to mRNA sorting and metabolism and indicate distinct roles for ZBP1 isoforms.
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DOI：
10.1073/pnas.240464097
发表时间：
2000-12-05
影响因子：
11.1
作者：
Brown, BA;Lowenhaupt, K;Rich, A
通讯作者：
Rich, A
影响因子：
5.3
作者：
Liu, H;Mulholland, N;Zhao, K
通讯作者：
Zhao, K
影响因子：
3.3
作者：
McInerney, GM;Kedersha, NL;Liljeström, P
通讯作者：
Liljeström, P
影响因子：
4.3
作者：
Parusel, I;Kahl, S;Koch-Nolte, F
通讯作者：
Koch-Nolte, F
影响因子：
5.6
作者：
Athanasiadis, A;Placido, D;Rich, A
通讯作者：
Rich, A