DOI: 10.5061/dryad.kkwh70s48
title: Dataset for: A structural signature motif enlightens the origin and diversification of nuclear receptors

description: Nuclear receptors are ligand-activated transcription factors that modulate
 gene regulatory networks from embryonic development to adult physiology
 and thus represent major targets for clinical interventions in many
 diseases. Most nuclear receptors function either as homodimers or as
 heterodimers. The dimerization is crucial for gene regulation by nuclear
 receptors, by extending the repertoire of binding sites in the promoters
 or the enhancers of target genes via combinatorial interactions. Here, we
 focused our attention on an unusual structural variation of the α-helix,
 called π-turn that is present in helix H7 of the ligand-binding domain of
 RXR and HNF4. By tracing back the complex evolutionary history of the
 π-turn, we demonstrate that it was present ancestrally and then
 independently lost in several nuclear receptor lineages. Importantly, the
 evolutionary history of the π-turn motif is parallel to the evolutionary
 diversification of the nuclear receptor dimerization ability from
 ancestral homodimers to derived heterodimers. We then carried out
 structural and biophysical analyses, in particular through point mutation
 studies of key RXR signature residues and showed that this motif plays a
 critical role in the network of interactions stabilizing homodimers. We
 further showed that the π-turn was instrumental in allowing a flexible
 heterodimeric interface of RXR in order to accommodate multiple interfaces
 with numerous partners and critical for the emergence of high affinity
 receptors. Altogether, our work allows to identify a functional role for
 the π-turn in oligomerization of nuclear receptors and reveals how this
 motif is linked to the emergence of a critical biological function. We
 conclude that the π-turn can be viewed as a structural exaptation that has
 contributed to enlarging the functional repertoire of nuclear receptors.
description: Ancestral character reconstruction and stochastic mapping were
 performed under R version 3.2.2 using the make.simmap function as
 implemented in the phytools package version 0.5.0. 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.
description: This dataset contains all the files necessary to reproduce Figure
 3 of the associated paper. Those file are: -
 script_Fig3.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_Fig3.nex: the backbone tree used for character
 mapping - Fig3A_RxxxE.csv: the data table containing
 the presence-absence data regarding the RxxxE motif for each nuclear
 receptor. Those characters were plotted on panel A of Figure 3.
 - Fig3B_dimerization.csv: the data table containing the data on
 dimerization modes accross nuclear receptors. Those character were plotted
 on panel B of Figure 3.