Dataset for FigS2F in "DNA is the allosteric driver for the asymmetric binding of homodimer estrogen-related receptor"

<strong>Abstract</strong> The estrogen-related receptors (ERRs, NR3B), orphan members of the steroid hormone receptor (SR) subfamily (NR3), are crucial for the transcriptional control of cellular energy metabolism. As basal members of NR3 subfamily, the ERRs are key elements for the understanding of how the binding of SRs to DNA evolved from monomeric to dimeric palindromic binding sites. To unravel the initial steps of DNA selection by SRs, we combined structural, biophysical and phylogenetic studies. Our results unveil the molecular mechanisms of the ERR dimerization which are imprinted in the protein itself with DNA acting as an allosteric driver by allowing the formation of a novel extended asymmetric dimerization region (KR-box). Phylogenetic analyses suggest that the dimerization asymmetry used by ERRs is an ancestral feature necessary for establishing a strong overall dimerization interface, which was progressively lost in the course evolution by other SRs. <strong>Methods</strong> Ancestral character reconstruction and stochastic mapping were performed under R version 4.1.2 using the make.simmap function as implemented in the phytools package version 1.0-1. Character evolution was inferred using a model of symmetrical transition rates between the character states (SYM). 10 000 character histories were sampled to allow the incorporation of the uncertainty associated with the transition between different states. Inferred state frequencies for ancestral nodes were plotted using the describe.simmap function. <strong>Usage Notes</strong> This dataset contains all the files necessary to reproduce Figure S2 of the associated paper (Patel et al., in preparation). Those files are: - script_FigS2F.R : the R script necessary to load the data and process them as indicated in the methods section. The outputs of character mappings are also indicated in the script file, in order that the user can compare them with the results he would get on his/her own computer. - tree_FigS2F.nex: the backbone tree used for character mapping - FigS2F_KR_box.csv: the data table containing the presence-absence data regarding the KR box motif for each nuclear receptor.**摘要** 雌激素相关受体（estrogen-related receptors, ERRs, NR3B）是类固醇激素受体（steroid hormone receptor, SR）超家族（NR3）的孤儿受体成员，在细胞能量代谢的转录调控中发挥关键作用。作为NR3超家族的基础成员，ERRs是解析类固醇激素受体与DNA的结合模式如何从单体结合演变为二聚体回文结合位点的核心研究对象。为阐明类固醇激素受体对DNA的识别起始步骤，本研究整合了结构生物学、生物物理学与系统发育学研究手段。研究结果揭示了ERR二聚化的分子机制：该机制内嵌于蛋白质自身结构中，DNA可通过促成新型延伸型不对称二聚化区域（KR-box）的形成，作为变构驱动因子调控该过程。系统发育分析表明，ERRs所采用的二聚化不对称性是一项祖先特征，该特征是形成稳定整体二聚化界面所必需的，而其他类固醇激素受体在演化历程中逐渐丢失了该特征。 **方法** 本研究基于R 4.1.2版本，借助phytools工具包1.0-1版本中内置的make.simmap函数，完成了祖先性状重建与随机映射分析。研究采用性状状态间对称转换速率模型（SYM）推断性状演化过程。共采样10000条性状演化历史，以纳入不同性状状态转换过程中存在的不确定性。借助describe.simmap函数，可绘制祖先节点的推断性状状态频率分布图。 **使用说明** 本数据集包含复现相关论文（Patel等，待发表）中图S2所需的全部文件，具体如下： - `script_FigS2F.R`：用于按照方法部分所述流程加载并处理数据的R脚本。脚本中同时标注了性状映射的预期输出结果，以便使用者将其与本地运行所得结果进行比对。 - `tree_FigS2F.nex`：用于性状映射的主干系统发育树文件。 - `FigS2F_KR_box.csv`：包含各核受体KR box基序有无情况的数据表。