Department of Biochemistry, Max Planck Institute for Developmental Biology, Spemannstrasse 35, 72076 Tübingen, Germany.
Institute of Biochemistry, ETH Zürich, Otto-Stern Weg 3, 8093 Zürich, Switzerland.
Curr Opin Struct Biol. 2017 Dec;47:40-51. doi: 10.1016/j.sbi.2017.05.009. Epub 2017 Jun 4.
Cellular mRNA levels are regulated via rates of transcription and decay. Since the removal of the mRNA 5'-cap by the decapping enzyme DCP2 is generally an irreversible step towards decay, it requires regulation. Control of DCP2 activity is likely effected by two interdependent means: by conformational control of the DCP2-DCP1 complex, and by assembly control of the decapping network, an array of mutually interacting effector proteins. Here, we compare three recent and conformationally distinct crystal structures of the DCP2-DCP1 decapping complex in the presence of substrate analogs and decapping enhancers and we discuss alternative substrate recognition modes for the catalytic domain of DCP2. Together with structure-based insight into decapping network assembly, we propose that DCP2-mediated decapping follows more than one path.
细胞 mRNA 水平通过转录和衰减速率进行调节。由于脱帽酶 DCP2 去除 mRNA 5' 帽通常是朝着衰减的不可逆步骤，因此它需要受到调控。DCP2 活性的控制可能通过两种相互依存的方式实现：通过 DCP2-DCP1 复合物的构象控制，以及通过去帽网络的组装控制，这是一系列相互作用的效应蛋白。在这里，我们比较了 DCP2-DCP1 去帽复合物在存在底物类似物和去帽增强剂时的三个最近的、构象不同的晶体结构，并讨论了 DCP2 催化结构域的替代底物识别模式。结合对去帽网络组装的结构见解，我们提出 DCP2 介导的去帽可能遵循不止一种途径。
