ArticleNature structural & molecular biology2022
Conformational buffering underlies functional selection in intrinsically disordered protein regions.
Article in Nature structural & molecular biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed.
- Article
- Multisite Threonine Phosphorylation in the SPT5 C-Terminal Region 1 Enables Sequence-Dependent Regulation without Global Structural Remodeling.The journal of physical chemistry. B · 2026Article
- AF-CALVADOS: AlphaFold-guided simulations of multi-domain proteins at the proteome level.Protein science : a publication of the Protein Society · 2026Article
- Molecular dynamics simulations of intrinsically disordered protein regions enable biophysical interpretation of variant-effect predictors.HGG advances · 2026Article
- Impact of N-terminal dimerization on formin homology 1 domain polymer dynamics and actin assembly.Biophysical journal · 2026Article
- The intrinsically disordered protein SPE-56 is required for acrosomal-like exocytosis and fertility in Caenorhabditis elegans.Scientific reports · 2026Article
- Generative design of intrinsically disordered protein regions with IDiom.bioRxiv : the preprint server for biology · 2026Article
- Toward a unified framework for determining conformational ensembles of disordered proteins.Nature methods · 2026Review
- Article
- STI1 domain engages transient helices to mediate Dsk2 phase separation and proteasome condensation.The EMBO journal · 2026Article
- Article
- Evolutionary turnover of key amino acids explains conservation of function without conservation of sequence in transcriptional activation domains.PLoS genetics · 2026Article
- Evolution of intrinsically disordered regions in vertebrate galectins for phase separation.EMBO reports · 2026Article
- Molecular grammars of predicted intrinsically disordered regions that span the human proteome.Cell · 2026Article
- IDPEnsembleTools: An open-source library for analysis of conformational ensembles of disordered proteins.Protein science : a publication of the Protein Society · 2026Article
- Decoding intrinsically disordered regions in biomolecular condensates.Fundamental research · 2026Review
- Mycobacterium tuberculosis uses intrinsically disordered, fast evolving proteins to interact with conserved host factors.Genome biology · 2025Article
- Impact of N-terminal dimerization on formin homology 1 domain polymer dynamics and actin assembly.bioRxiv : the preprint server for biology · 2025Article
- Functional and Structural Determinants of Long- and Short-Term Evolution of Herpesvirus Proteins.Molecular biology and evolution · 2025Article
- The intrinsically disordered regions of organellophagy receptors are interchangeable and control organelle fragmentation, ER-phagy and mitophagy flux.Nature cell biology · 2025Article
8 more citing papers are in PubMed but not listed here.
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19 authors.
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Abstract
Many disordered proteins conserve essential functions in the face of extensive sequence variation, making it challenging to identify the mechanisms responsible for functional selection. Here we identify the molecular mechanism of functional selection for the disordered adenovirus early gene 1A (E1A) protein. E1A competes with host factors to bind the retinoblastoma (Rb) protein, subverting cell cycle regulation. We show that two binding motifs tethered by a hypervariable disordered linker drive picomolar affinity Rb binding and host factor displacement. Compensatory changes in amino acid sequence composition and sequence length lead to conservation of optimal tethering across a large family of E1A linkers. We refer to this compensatory mechanism as conformational buffering. We also detect coevolution of the motifs and linker, which can preserve or eliminate the tethering mechanism. Conformational buffering and motif-linker coevolution explain robust functional encoding within hypervariable disordered linkers and could underlie functional selection of many disordered protein regions.
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