Dcp1对Dcp2的识别与激活的结构基础。
Structural basis of dcp2 recognition and activation by dcp1.
作者信息
She Meipei, Decker Carolyn J, Svergun Dmitri I, Round Adam, Chen Nan, Muhlrad Denise, Parker Roy, Song Haiwei
机构信息
Laboratory of Macromolecular Structure, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, 61 Biopolis Drive, Proteos, 138673 Singapore.
出版信息
Mol Cell. 2008 Feb 15;29(3):337-49. doi: 10.1016/j.molcel.2008.01.002.
A critical step in mRNA degradation is the removal of the 5' cap structure, which is catalyzed by the Dcp1-Dcp2 complex. The crystal structure of an S. pombe Dcp1p-Dcp2n complex combined with small-angle X-ray scattering analysis (SAXS) reveals that Dcp2p exists in open and closed conformations, with the closed complex being, or closely resembling, the catalytically more active form. This suggests that a conformational change between these open and closed complexes might control decapping. A bipartite RNA-binding channel containing the catalytic site and Box B motif is identified with a bound ATP located in the catalytic pocket in the closed complex, suggesting possible interactions that facilitate substrate binding. Dcp1 stimulates the activity of Dcp2 by promoting and/or stabilizing the closed complex. Notably, the interface of Dcp1 and Dcp2 is not fully conserved, explaining why the Dcp1-Dcp2 interaction in higher eukaryotes requires an additional factor.
mRNA降解的关键步骤是去除5'帽结构，这一过程由Dcp1-Dcp2复合物催化。粟酒裂殖酵母Dcp1p-Dcp2n复合物的晶体结构结合小角X射线散射分析（SAXS）表明，Dcp2p存在开放和封闭两种构象，其中封闭复合物是或非常类似于催化活性更高的形式。这表明这些开放和封闭复合物之间的构象变化可能控制去帽过程。一个包含催化位点和Box B基序的双RNA结合通道被确定，在封闭复合物的催化口袋中有一个结合的ATP，这表明可能存在促进底物结合的相互作用。Dcp1通过促进和/或稳定封闭复合物来刺激Dcp2的活性。值得注意的是，Dcp1和Dcp2的界面并不完全保守，这解释了为什么高等真核生物中Dcp1-Dcp2相互作用需要一个额外的因子。
Zotero 插件