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Article
Open AccessRational optimization of a transcription factor activation domain inhibitor
Transcription factors are among the most attractive therapeutic targets but are considered largely ‘undruggable’ in part due to the intrinsically disordered nature of their activation domains. Here we show tha...
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Article
Open AccessA MEC-2/stomatin condensate liquid-to-solid phase transition controls neuronal mechanotransduction during touch sensing
A growing body of work suggests that the material properties of biomolecular condensates ensuing from liquid–liquid phase separation change with time. How this aging process is controlled and whether the conde...
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Article
Open AccessGEMC1 and MCIDAS interactions with SWI/SNF complexes regulate the multiciliated cell-specific transcriptional program
Multiciliated cells (MCCs) project dozens to hundreds of motile cilia from their apical surface to promote the movement of fluids or gametes in the mammalian brain, airway or reproductive organs. Differentiati...
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Article
Open AccessAberrant phase separation and nucleolar dysfunction in rare genetic diseases
Thousands of genetic variants in protein-coding genes have been linked to disease. However, the functional impact of most variants is unknown as they occur within intrinsically disordered protein regions that ...
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Article
Open AccessA glutamine-based single α-helix scaffold to target globular proteins
The binding of intrinsically disordered proteins to globular ones can require the folding of motifs into α-helices. These interactions offer opportunities for therapeutic intervention but their modulation with...
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Article
Open AccessSmall molecules targeting the disordered transactivation domain of the androgen receptor induce the formation of collapsed helical states
Intrinsically disordered proteins, which do not adopt well-defined structures under physiological conditions, are implicated in many human diseases. Small molecules that target the disordered transactivation d...
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Article
Nucleus-translocated mitochondrial cytochrome c liberates nucleophosmin-sequestered ARF tumor suppressor by changing nucleolar liquid–liquid phase separation
The regular functioning of the nucleolus and nucleus-mitochondria crosstalk are considered unrelated processes, yet cytochrome c (Cc) migrates to the nucleus and even the nucleolus under stress conditions. Nucleo...
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Protocol
Intrinsically Disordered Proteins (IDP): Purification Under Denaturing Conditions
Recombinant protein expression in E. coli often induces the expressed protein to accumulate in insoluble aggregates, named inclusion bodies (IBs), that represent easy to isolate, highly pure protein reservoirs. I...
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Article
Evolution of a histone variant involved in compartmental regulation of NAD metabolism
NAD metabolism is essential for all forms of life. Compartmental regulation of NAD+ consumption, especially between the nucleus and the mitochondria, is required for energy homeostasis. However, how compartmental...
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Protocol
Recombinant Production of Monomeric Isotope-Enriched Aggregation-Prone Peptides: Polyglutamine Tracts and Beyond
High solvent exposure of certain sequences located in intrinsically disordered regions (IDRs) may eventually lead to aggregation, as is the case for some low-complexity regions (LCRs) and short linear motifs (...
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Article
Open AccessAuthor Correction: Hsp70 and Hsp40 inhibit an inter-domain interaction necessary for transcriptional activity in the androgen receptor
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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Article
Open AccessThe structure of a polygamous repressor reveals how phage-inducible chromosomal islands spread in nature
Stl is a master repressor encoded by Staphylococcus aureus pathogenicity islands (SaPIs) that maintains integration of these elements in the bacterial chromosome. After infection or induction of a resident helper...
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Article
Open AccessHsp70 and Hsp40 inhibit an inter-domain interaction necessary for transcriptional activity in the androgen receptor
Molecular chaperones such as Hsp40 and Hsp70 hold the androgen receptor (AR) in an inactive conformation. They are released in the presence of androgens, enabling transactivation and causing the receptor to be...
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Article
Open AccessSide chain to main chain hydrogen bonds stabilize a polyglutamine helix in a transcription factor
Polyglutamine (polyQ) tracts are regions of low sequence complexity frequently found in transcription factors. Tract length often correlates with transcriptional activity and expansion beyond specific threshol...
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Article
Open AccessApplication of Lysine-specific Labeling to Detect Transient Interactions Present During Human Lysozyme Amyloid Fibril Formation
Populating transient and partially unfolded species is a crucial step in the formation and accumulation of amyloid fibrils formed from pathogenic variants of human lysozyme linked with a rare but fatal heredit...
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Article
Open AccessFoxA and LIPG endothelial lipase control the uptake of extracellular lipids for breast cancer growth
The mechanisms that allow breast cancer (BCa) cells to metabolically sustain rapid growth are poorly understood. Here we report that BCa cells are dependent on a mechanism to supply precursors for intracellula...
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Article
Correlated motions are a fundamental property of β-sheets
Correlated motions in proteins can mediate fundamental biochemical processes such as signal transduction and allostery. The mechanisms that underlie these processes remain largely unknown due mainly to limitat...
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Article
Peptide nanofibrils boost retroviral gene transfer and provide a rapid means for concentrating viruses
Inefficient gene transfer and low virion concentrations are common limitations of retroviral transduction1. We and others have previously shown that peptides derived from human semen form amyloid fibrils that boo...
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Article
Open AccessUnderstanding biomolecular motion, recognition, and allostery by use of conformational ensembles
We review the role conformational ensembles can play in the analysis of biomolecular dynamics, molecular recognition, and allostery. We introduce currently available methods for generating ensembles of biomole...
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Article
The MUMO (minimal under-restraining minimal over-restraining) method for the determination of native state ensembles of proteins
While reliable procedures for determining the conformations of proteins are available, methods for generating ensembles of structures that also reflect their flexibility are much less well established. Here we...
