Similar to other GPCRs, in the structure of the TSHR TMD, the ionic lock between Arg5193.50 in TM3 and Asp6196.30 in TM6 is present in the inactive state and absent in the active state.
Next, we explored whether the independent association of PRCa genes with PRC and S5p (in the PRC-repressed state), or with S2p and S5p (in the active state), could be related to natural fluctuations in transcription factor levels across the heterogeneous ESC population.
In contrast, in our models the proposed additional interactions produced by V421 and L665 in the active state of the receptor would be weakened by substitutions with the residues with smaller side chains.
In this model, τ(t) can take one of two values depending if the gene is actively transcribing, namely τ0 when transcription is only occurring at a basal level and τ1 in the active state.
A common feature of PcG target genes and their PREs in the active state is that they bind ASH1 and N-terminal but not C-terminal of TRX.
At the time of the study, the experimental structures of 18 different inactive GPCRs and three structures in the active state were available from the PDB.
Each population is subject to an external driving given by independent Poisson spike trains, resulting from 100 excitatory neurons, at rate r = 15.4 Hz on each neuron in the passive state, and 16.3 Hz in the active state.
For example, one of the most common Ras mutations is a glycine to valine mutation at residue 12 (Ras V 12) which renders Ras insensitive to inactivation by Ras-GAP and thus locked in the active state [ 26].
DOI: http://dx.doi.org/10.7554/eLife.03772.020 The most likely explanation for the ligand-independent activity of IGF1R variants with single cysteine substitutions is that IGF1R samples the active conformation in the absence of ligand and becomes trapped in the active state by a disulfide bond.
The in vivo chromatin structure of SNR6 is reported to have an array of positioned nucleosomes upstream of the TATA box and downstream of A box, flanking a nucleosome-free region between TATA box and A box in the active state of the gene [ 37, 39].
