Unstructured transcription factor interactions enable emergent specificity How intrinsically disordered regions (IDRs) influence chromatin binding and nuclear organization of transcription factors (TFs) remains unclear. We employed proximity-assisted photoactivation (PAPA), ...

While #DNAbindingdomains & #IntrinsicallyDisorderedRegions individually do not show binding specificity, "ensembles of diverse, unstructured interactions" collectively enable emergent #TranscriptionFactor specificity ➡️ www.science.org/doi/10.1126/...
#generegulation #IDRs #TFspecificity #chromatin

Top: The sequences and features of the Rim4 intrinsically disordered region (IDR) are rapidly evolving. Distribution of charged residues and RRM domains is plotted next to a phylogenetic tree of analyzed yeast species. The phylogenetic tree was built using PhytoT based on NCBI phylogenetic data and was visualized using interactive tree of life (iTOL) software [93]. RRM domains are colored light blue. Acidic residues (D, E) are colored in red and basic residues (R, K) in blue. Bottom: Schematic model showing how natural selection on the hydrophobicity of the Rim4 IDR could govern its ability to act as both a translational activator and repressor. Each function requires IDR hydrophobicity within a distinct, partially overlapping range. In Saccharomyces cerevisiae and fully complementing orthologs, hydrophobicity resides in the intersection of both optimal windows (top left). Directional selection toward one function’s optimum (top right, bottom left)—such as stronger repressor activity—shifts hydrophobicity out of the activator window and impairs that activity. Upon loss of sporulation (bottom right), selective constraints on both functions are relaxed, allowing hydrophobicity (and consequently both activities) to drift and decay.

#IntrinsicallyDisorderedRegions (IDRs) in #proteins lack stable structure & conserved sequence. This study uses cross-species rescue of yeast Rim4 to show how evolutionary pressure on #IDRs can favor biochemical traits underlying distinct functions across 100s My @plosbiology.org 🧪 plos.io/4gKBYVH

Top: The sequences and features of the Rim4 intrinsically disordered region (IDR) are rapidly evolving. Distribution of charged residues and RRM domains is plotted next to a phylogenetic tree of analyzed yeast species. The phylogenetic tree was built using PhytoT based on NCBI phylogenetic data and was visualized using interactive tree of life (iTOL) software [93]. RRM domains are colored light blue. Acidic residues (D, E) are colored in red and basic residues (R, K) in blue. Bottom: Schematic model showing how natural selection on the hydrophobicity of the Rim4 IDR could govern its ability to act as both a translational activator and repressor. Each function requires IDR hydrophobicity within a distinct, partially overlapping range. In Saccharomyces cerevisiae and fully complementing orthologs, hydrophobicity resides in the intersection of both optimal windows (top left). Directional selection toward one function’s optimum (top right, bottom left)—such as stronger repressor activity—shifts hydrophobicity out of the activator window and impairs that activity. Upon loss of sporulation (bottom right), selective constraints on both functions are relaxed, allowing hydrophobicity (and consequently both activities) to drift and decay.

#IntrinsicallyDisorderedRegions (IDRs) in #proteins lack stable structure & conserved sequence. This study uses cross-species rescue of yeast Rim4 to show how evolutionary pressure on #IDRs can favor biochemical traits underlying distinct functions across 100s My @plosbiology.org 🧪 plos.io/4gKBYVH

Top: The sequences and features of the Rim4 intrinsically disordered region (IDR) are rapidly evolving. Distribution of charged residues and RRM domains is plotted next to a phylogenetic tree of analyzed yeast species. The phylogenetic tree was built using PhytoT based on NCBI phylogenetic data and was visualized using interactive tree of life (iTOL) software [93]. RRM domains are colored light blue. Acidic residues (D, E) are colored in red and basic residues (R, K) in blue. Bottom: Schematic model showing how natural selection on the hydrophobicity of the Rim4 IDR could govern its ability to act as both a translational activator and repressor. Each function requires IDR hydrophobicity within a distinct, partially overlapping range. In Saccharomyces cerevisiae and fully complementing orthologs, hydrophobicity resides in the intersection of both optimal windows (top left). Directional selection toward one function’s optimum (top right, bottom left)—such as stronger repressor activity—shifts hydrophobicity out of the activator window and impairs that activity. Upon loss of sporulation (bottom right), selective constraints on both functions are relaxed, allowing hydrophobicity (and consequently both activities) to drift and decay.

#IntrinsicallyDisorderedRegions (IDRs) in #proteins lack stable structure & conserved sequence. This study uses cross-species rescue of yeast Rim4 to show how evolutionary pressure on #IDRs can favor biochemical traits underlying distinct functions across 100s My @plosbiology.org 🧪 plos.io/4gKBYVH

Online now - the Review "Intrinsic disorder and fuzzy interactions drive multiple functions of #HMGB1" from Giovanna Musco, Marco Emilio Bianchi, et al.

#FuzzyComplexes #IntrinsicallyDisorderedRegions #Multivalency #MolecularChaperone

authors.elsevier.com/sd/article/S...