Structural Insights into the Interaction Between CRTCs and 14-3-3
Structural Insights into the Interaction Between CRTCs and 14-3-3
复制标题
CRTC 与 14-3-3 之间相互作用的结构洞察
DOI：
10.1016/j.jmb.2021.166874
复制
发表时间：
2021-02-19
影响因子：
5.6
通讯作者：
Xiang, Song
中科院分区：
文献类型：
--
作者：
Chen, Hetao;Zhang, Hang;Xiang, Song
CREB调节转录辅激活因子（CREB Regulated Transcriptional Coactivators，CRTCs）调节CREB靶基因的转录，在许多生物学过程中发挥重要作用。在基础状态下，它们在多个残基处被磷酸化，这促进了它们与14-3-3的缔合，14-3-3将它们隔离在细胞质中。在去磷酸化后，它们移位到细胞核中并与CREB结合以激活靶基因转录。尽管CRTCs中的三个保守丝氨酸残基参与了它们的磷酸化调节，但它们是否以及如何介导与14-3-3的相互作用尚不清楚。在这里，我们提供了直接的证据表明，这些残基和侧翼区域与14-3-3相互作用和相互作用的结构基础。我们的研究还确定了CRTC 1中一个新的盐桥，它在结合14-3-3中具有重要功能，扩展了对14-3-3与其配体之间相互作用的理解。(C)2021爱思唯尔有限公司保留所有权利。
The CREB-Regulated Transcriptional Coactivators (CRTCs) regulate the transcription of CREB target genes and have important functions in many biological processes. At the basal state, they are phosphorylated at multiple residues, which promotes their association with 14-3-3 that sequesters them in the cytoplasm. Upon dephosphorylation, they translocate into the nuclei and associate with CREB to activate the target gene transcription. Although three conserved serine residues in CRTCs have been implicated in their phosphorylation regulation, whether and how they mediate interactions with 14-3-3 is unclear. Here, we provide direct evidence that these residues and flanking regions interact with 14-3-3 and the structural basis of the interaction. Our study also identified a novel salt bridge in CRTC1 with an important function in binding 14-3-3, expanding the understanding of the interaction between 14-3-3 and its ligands. (C) 2021 Elsevier Ltd. All rights reserved.