Jeske Mandy, Müller Christoph W, Ephrussi Anne
Developmental Biology Unit, European Molecular Biology Laboratory, 69117 Heidelberg, Germany.
Structural and Computational Biology Unit, European Molecular Biology Laboratory, 69117 Heidelberg, Germany.
Genes Dev. 2017 May 1;31(9):939-952. doi: 10.1101/gad.297051.117. Epub 2017 May 23.
DEAD-box RNA helicases play important roles in a wide range of metabolic processes. Regulatory proteins can stimulate or block the activity of DEAD-box helicases. Here, we show that LOTUS (Limkain, Oskar, and Tudor containing proteins 5 and 7) domains present in the germline proteins Oskar, TDRD5 (Tudor domain-containing 5), and TDRD7 bind and stimulate the germline-specific DEAD-box RNA helicase Vasa. Our crystal structure of the LOTUS domain of Oskar in complex with the C-terminal RecA-like domain of Vasa reveals that the LOTUS domain occupies a surface on a DEAD-box helicase not implicated previously in the regulation of the enzyme's activity. We show that, in vivo, the localization of Vasa to the nuage and germ plasm depends on its interaction with LOTUS domain proteins. The binding and stimulation of Vasa DEAD-box helicases by LOTUS domains are widely conserved.
DEAD盒RNA解旋酶在广泛的代谢过程中发挥重要作用。调节蛋白可以刺激或阻断DEAD盒解旋酶的活性。在这里，我们表明，生殖系蛋白奥斯卡、TDRD5（含Tudor结构域5）和TDRD7中存在的LOTUS（含Limkain、Oskar和Tudor蛋白5和7）结构域结合并刺激生殖系特异性DEAD盒RNA解旋酶Vasa。我们解析的奥斯卡LOTUS结构域与Vasa的C端类RecA结构域复合物的晶体结构表明，LOTUS结构域占据了DEAD盒解旋酶上一个以前未涉及该酶活性调节的表面。我们表明，在体内，Vasa定位于生殖质和生殖粒取决于它与LOTUS结构域蛋白的相互作用。LOTUS结构域对Vasa DEAD盒解旋酶的结合和刺激作用具有广泛的保守性。
