Biology subjects

Sukenik, S.

Publications and source records attributed to Sukenik, S..

22 records · Page 2Linked to original sources

bioRxiv2020

Probing the Hidden Sensitivity of Intrinsically Disordered Proteins to their Chemical Environment

Intrinsically disordered proteins and protein-regions (IDRs) make up roughly 30% of the human proteome and play vital roles in a wide variety of biological processes. Given a lack of persistent tertiary structure, all of the residues in an IDR are, to some extent, solvent exposed. This extensive surface area, coupled with the absence of strong intramolecular contacts, makes IDRs inherently sensitive to their chemical environment. Despite this sensitivity, our understanding of how IDR structural ensembles are influenced by changes in their chemical environment is limited. This is particularly relevant given a growing body of evidence showing that IDR function is linked to the underlying structural ensemble. We develop and use a combined experimental, computational, and analytical framework for high-throughput characterization of IDR sensitivity we call solution space scanning. Our framework reveals that IDRs show sequence-dependent sensitivity to solution chemistry, with complex behavior that can be interpreted through relatively simple polymer models. Our results imply that solution-responsive IDRs are ubiquitous and can provide an additional layer of biological regulation.

biophysics↗

bioRxiv2020

Hydration-dependent phase separation of a prion-like protein regulates seed germination during water stress.

Many organisms evolved strategies to survive and thrive under extreme desiccation. Plant seeds protect dehydrated embryos from a variety of stressors and can even lay dormant for millennia. While hydration is the key trigger that reactivates metabolism and kick-starts germination, the exact mechanism by which the embryo senses water remains unresolved. We identified an uncharacterized Arabidopsis thaliana prion-like protein we named FLOE1, which phase separates upon hydration and allows the embryo to sense water stress. We demonstrate that the biophysical states of FLOE1 condensates modulate its biological function in vivo in suppressing seed germination under unfavorable environments. We also find intragenic, intraspecific, and interspecific natural variations in phase separation propensity of FLOE1 homologs. These findings demonstrate a physiological role of phase separation in a multicellular organism and have direct implications for plant ecology and agriculture, especially the design of drought resistant crops, in the face of climate change.

cell biology↗

bioRxiv2019

Controlling Structural Bias in Intrinsically Disordered Proteins Using Solution Space Scanning

Intrinsically disordered proteins or regions (IDRs) differ from their well-folded counterparts by lacking a stable tertiary state. Instead, IDRs exist in an ensemble of conformations and often possess localized, loosely held residual structure that can be a key determinant of their activity. With no extensive network of non-covalent bonds and a high propensity for exposed surface areas, the various features of an IDRs ensemble - including local residual structure and global conformational biases - are an emergent property of both the amino acid sequence and the solution environment. Here, we attempt to understand how shifting solution conditions can alter an IDRs ensemble. We present an efficient computational method to alter solution-protein interactions we term Solution Space (SolSpace) Scanning. SolSpace scanning uses all-atom Monte-Carlo simulations to construct ensembles under a wide range of distinct solution conditions. By tuning the interactions of specific protein moieties with the solution in a systematic manner we can both enhance and reduce local residual structure. This approach allows the design of distinct residual structures in IDRs, offering an alternative approach to mutational studies for exploring sequence-to-ensemble relationships. Our results raise the possibility of solution-based regulation of protein functions both outside and within the dynamic solution environment of cells.

biophysics↗

bioRxiv2018

Phase Separation of YAP Reprograms Cells for Long-term YAP Target Gene Expression

Yes-associated Protein (YAP) is a transcriptional co-activator that regulates cell proliferation and survival by binding to a selective set of enhancers for potent target gene activation, but how YAP coordinates these transcriptional responses is unknown. Here, we demonstrate that YAP forms liquid-like condensates in the nucleus in response to macromolecular crowding. Formed within seconds of hyperosmotic stress, YAP condensates compartmentalized YAPs DNA binding cofactor TEAD1 along with other YAP-related transcription co-activators, including TAZ, and subsequently induced transcription of YAP-specific proliferation genes. Super-resolution imaging using Assay for Transposase Accessible Chromatin with photoactivated localization microscopy (ATAC-PALM) revealed that YAP nuclear condensates were areas enriched in accessible chromatin domains organized as super-enhancers. Initially devoid of RNA Polymerase II (Pol II), the accessible chromatin domains later acquired Pol II, producing newly transcribed RNA. Removal of YAPs intrinsically-disordered transcription activation domain (TAD) prevented YAP condensate formation and diminished downstream YAP signaling. Thus, dynamic changes in genome organization and gene activation during YAP reprogramming is mediated by liquid-liquid phase separation.

cell biology↗