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

Abstract

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.

Methods

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.

Usage Notes

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.