Center for Proteome Biophysics, DGIST, Daegu 42988, Korea; Department of Physics, Pusan National University, Busan 46241, Korea.
Center for Plant Aging Research, Institute for Basic Science, Daegu 42988, Korea.
Cell Rep. 2018 Jan 30;22(5):1141-1150. doi: 10.1016/j.celrep.2018.01.002.
The affinity of transcription factors (TFs) for their target DNA is a critical determinant of gene expression. Whether the DNA-binding domain (DBD) of TFs alone can regulate binding affinity to DNA is an important question for identifying the design principle of TFs. We studied ANAC019, a member of the NAC TF family of proteins in Arabidopsis, and found a well-conserved histidine switch located in its DBD, which regulates both homodimerization and transcriptional control of the TF through H135 protonation. We found that the removal of a C-terminal intrinsically disordered region (IDR) in the TF abolished the pH-dependent binding of the N-terminal DBD to DNA. We propose a mechanism in which long-range electrostatic interactions between DNA and the negatively charged C-terminal IDR turns on the pH dependency of the DNA-binding affinity of the N-terminal DBD.
转录因子 (TFs) 与它们的靶 DNA 的亲和力是基因表达的一个关键决定因素。TFs 的 DNA 结合结构域 (DBD) 本身是否可以调节与 DNA 的结合亲和力，这是确定 TF 设计原则的一个重要问题。我们研究了拟南芥 NAC TF 家族蛋白中的 ANAC019，发现其 DBD 中存在一个保守的组氨酸开关，通过 H135 质子化来调节 TF 的同源二聚化和转录调控。我们发现，TF 中 C 端无规卷曲结构域 (IDR) 的缺失消除了 N 端 DBD 与 DNA 之间 pH 依赖性的结合。我们提出了一种机制，即 DNA 与带负电荷的 C 端 IDR 之间的长程静电相互作用使 N 端 DBD 与 DNA 的结合亲和力对 pH 具有依赖性。
