Matches in SemOpenAlex for { <https://semopenalex.org/work/W4225415044> ?p ?o ?g. }
Showing items 1 to 63 of
63
with 100 items per page.
- W4225415044 abstract "Elucidating the molecular rules of ligand-induced phase transitions is essential to determining the regulation of the formation and disassembly of biomolecular condensates. Ubiquitin-binding shuttle protein Ubiquilin-2 (UBQLN2) undergoes liquid-liquid phase separation (LLPS) in vitro and colocalizes into stress-induced cytoplasmic puncta in vivosuch as stress granules.[1] A recent study from our lab indicated that ubiquitin (Ub), and compact polyUb chains such as K48- & K11-Ub4 can inhibit UBQLN2 LLPS by binding to phase separation-driving UBQLN2 stickers whereas more extended chains such as K63- & M1-Ub4 can promote UBQLN2 phase separation over a large Ub:UBQLN2 range by acting as a multivalent ligand scaffold.[2] Using a designed tetrameric ubiquitin construct (HOTag6-Ub) that resembles a multi-monoubiquitinated substrate, we further probed how alterations to the stickers and spacers of the HOTag6-Ub ligand can modulate UBQLN2 phase behavior. Using turbidity and microscopy experiments, we obtained phase diagrams for LLPS driven by heterotypic interactions between UBQLN2 and HOTag6-Ub. We discovered that, by changing the length and flexibility of the linker that tethers the Ub units to HOTag6, we can tune UBQLN2 LLPS. Single- and double-point mutations to the Ub hydrophobic binding surface (I44 & V70 stickers) decreased the binding affinity between Ub and UBQLN2, thereby leading to changes in the shape of HOTag6-Ub/UBQLN2 phase diagrams. Using nuclear magnetic resonance spectroscopy (NMR), microscopy and UV-Vis spectroscopic methods we demonstrated that linker conformation, linker flexibility, and interactions with the Ub binding surface are driving factors of UBQLN2/HOTag6-Ub co-phase separation. Overall, our findings highlight how multivalent ligands can tune phase separation behavior of protein systems. [1] Dao, T. P., Kolaitis, R.-M., Kim, H. J., O'Donovan, K., Martyniak, B., Colicino, E., Hehnly, H., Taylor, J. P., and Castañeda, C. A. (2018). Ubiquitin Modulates Liquid-Liquid Phase Separation of UBQLN2 via Disruption of Multivalent Interactions. Mol. Cell 69, 965-978. [2] Dao, T. P., Yang, Y., Cosgrove, M. S., Hopkins, J. B., Ma, W., Castaneda, C. A. (2021). Mechanistic insights into the enhancement or inhibition of phase separation by polyubiquitin chains of different lengths or linkages. bioRxiv 2021.11.12.467822; doi: https://doi.org/10.1101/2021.11.12.467822." @default.
- W4225415044 created "2022-05-05" @default.
- W4225415044 creator A5019107872 @default.
- W4225415044 creator A5031525806 @default.
- W4225415044 creator A5078087254 @default.
- W4225415044 date "2022-05-01" @default.
- W4225415044 modified "2023-09-27" @default.
- W4225415044 title "Effects of Modulating Multivalent Ligand Binding Accessibility & Affinity on Liquid‐Liquid Phase Separation" @default.
- W4225415044 doi "https://doi.org/10.1096/fasebj.2022.36.s1.r6323" @default.
- W4225415044 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/35554141" @default.
- W4225415044 hasPublicationYear "2022" @default.
- W4225415044 type Work @default.
- W4225415044 citedByCount "0" @default.
- W4225415044 crossrefType "journal-article" @default.
- W4225415044 hasAuthorship W4225415044A5019107872 @default.
- W4225415044 hasAuthorship W4225415044A5031525806 @default.
- W4225415044 hasAuthorship W4225415044A5078087254 @default.
- W4225415044 hasConcept C104317684 @default.
- W4225415044 hasConcept C111919701 @default.
- W4225415044 hasConcept C116569031 @default.
- W4225415044 hasConcept C12554922 @default.
- W4225415044 hasConcept C170493617 @default.
- W4225415044 hasConcept C185592680 @default.
- W4225415044 hasConcept C25602115 @default.
- W4225415044 hasConcept C2780557392 @default.
- W4225415044 hasConcept C41008148 @default.
- W4225415044 hasConcept C55493867 @default.
- W4225415044 hasConcept C8010536 @default.
- W4225415044 hasConcept C86803240 @default.
- W4225415044 hasConceptScore W4225415044C104317684 @default.
- W4225415044 hasConceptScore W4225415044C111919701 @default.
- W4225415044 hasConceptScore W4225415044C116569031 @default.
- W4225415044 hasConceptScore W4225415044C12554922 @default.
- W4225415044 hasConceptScore W4225415044C170493617 @default.
- W4225415044 hasConceptScore W4225415044C185592680 @default.
- W4225415044 hasConceptScore W4225415044C25602115 @default.
- W4225415044 hasConceptScore W4225415044C2780557392 @default.
- W4225415044 hasConceptScore W4225415044C41008148 @default.
- W4225415044 hasConceptScore W4225415044C55493867 @default.
- W4225415044 hasConceptScore W4225415044C8010536 @default.
- W4225415044 hasConceptScore W4225415044C86803240 @default.
- W4225415044 hasFunder F4320306076 @default.
- W4225415044 hasFunder F4320306232 @default.
- W4225415044 hasFunder F4320332161 @default.
- W4225415044 hasIssue "S1" @default.
- W4225415044 hasLocation W42254150441 @default.
- W4225415044 hasLocation W42254150442 @default.
- W4225415044 hasOpenAccess W4225415044 @default.
- W4225415044 hasPrimaryLocation W42254150441 @default.
- W4225415044 hasRelatedWork W1965702897 @default.
- W4225415044 hasRelatedWork W1969940393 @default.
- W4225415044 hasRelatedWork W2002032965 @default.
- W4225415044 hasRelatedWork W2032540338 @default.
- W4225415044 hasRelatedWork W2050940716 @default.
- W4225415044 hasRelatedWork W2095380224 @default.
- W4225415044 hasRelatedWork W2739417245 @default.
- W4225415044 hasRelatedWork W2912369664 @default.
- W4225415044 hasRelatedWork W2952991618 @default.
- W4225415044 hasRelatedWork W4230779809 @default.
- W4225415044 hasVolume "36" @default.
- W4225415044 isParatext "false" @default.
- W4225415044 isRetracted "false" @default.
- W4225415044 workType "article" @default.