Zinc fingers can act as Zn2+ sensors to regulate transcriptional activation domain function
Zinc fingers can act as Zn2+ sensors to regulate transcriptional activation domain function
复制标题
DOI：
10.1093/emboj/cdg484
复制
发表时间：
2003-10-01
期刊：
影响因子：
11.4
通讯作者：
Eide, DJ
中科院分区：
文献类型：
--
作者：
Bird, AJ;McCall, K;Eide, DJ
酵母Zap1转录因子控制锌积累和储存相关基因的表达。ZAP1在锌限制的细胞中是活性的，而在充足的细胞中是被抑制的。ZAP1有两个激活结构域，即AD1和AD2，它们都受锌的调节。AD2的功能被定位到一个区域，该区域包含两个半胱氨酸(2)组氨酸(2)锌指，ZF1和ZF2，它们不参与DNA结合。更详细的定位将AD2几乎精确地放置在ZF2的端点内，表明这些手指在调节激活结构域功能中发挥了作用。与这一假设一致，ZF1和ZF2在体外与锌结合，但不如参与DNA结合的锌指稳定。此外，预测会破坏锌与ZF1和/或ZF2结合的突变使AD2具有结构性活性。我们的结果还表明，抑制形式的AD2需要ZF1和ZF2之间的分子内相互作用。这些研究表明，这些锌指作为锌传感器发挥了前所未有的作用，控制激活结构域功能。
The yeast Zap1 transcription factor controls the expression of genes involved in zinc accumulation and storage. Zap1 is active in zinc-limited cells and repressed in replete cells. Zap1 has two activation domains, AD1 and AD2, which are both regulated by zinc. AD2 function was mapped to a region containing two Cys(2)His(2) zinc fingers, ZF1 and ZF2, that are not involved in DNA binding. More detailed mapping placed AD2 almost precisely within the endpoints of ZF2, suggesting a role for these fingers in regulating activation domain function. Consistent with this hypothesis, ZF1 and ZF2 bound zinc in vitro but less stably than did zinc fingers involved in DNA binding. Furthermore, mutations predicted to disrupt zinc binding to ZF1 and/or ZF2 rendered AD2 constitutively active. Our results also indicate that the repressed form of AD2 requires an intramolecular interaction between ZF1 and ZF2. These studies suggest that these zinc fingers play an unprecedented role as zinc sensors to control activation domain function.