Enzymatic Reactions inside Biological Condensates

Zhang, Yi; Narlikar, Geeta J.; Kutateladze, Tatiana G.

doi:10.1016/j.jmb.2020.08.009

Cited by 63 publications

(52 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We examined the effect of phase separation on enzymatic activity and histone substrate selectivity of p300 BRPHZ . Because phase separation conditions can promote enzymatic reactions owing to higher local concentrations of both the enzyme and substrate 44 , we initially thought that p300 HAT activity would also be elevated due to increased local concentration of p300 BRPHZ and the substrate, either p300 BRPHZ and/or NCP inside the droplets. On the other hand, the intermolecular AIL–HAT interaction, which leads to the formation of p300 condensates, physically blocks the active site of the HAT domain and thus would lead to a reduction in the enzymatic activity, similar to what was observed for the TOR kinase 45 .…”

Section: Resultsmentioning

confidence: 99%

Nuclear condensates of p300 formed though the structured catalytic core can act as a storage pool of p300 with reduced HAT activity

Zhang

Brown

et al. 2021

Nat Commun

Self Cite

View full text Add to dashboard Cite

The transcriptional co-activator and acetyltransferase p300 is required for fundamental cellular processes, including differentiation and growth. Here, we report that p300 forms phase separated condensates in the cell nucleus. The phase separation ability of p300 is regulated by autoacetylation and relies on its catalytic core components, including the histone acetyltransferase (HAT) domain, the autoinhibition loop, and bromodomain. p300 condensates sequester chromatin components, such as histone H3 tail and DNA, and are amplified through binding of p300 to the nucleosome. The catalytic HAT activity of p300 is decreased due to occlusion of the active site in the phase separated droplets, a large portion of which co-localizes with chromatin regions enriched in H3K27me3. Our findings suggest a model in which p300 condensates can act as a storage pool of the protein with reduced HAT activity, allowing p300 to be compartmentalized and concentrated at poised or repressed chromatin regions.

show abstract

Section: Resultsmentioning

confidence: 99%

Nuclear condensates of p300 formed though the structured catalytic core can act as a storage pool of p300 with reduced HAT activity

Zhang

Brown

et al. 2021

Nat Commun

Self Cite

View full text Add to dashboard Cite

show abstract

“…Condensates have properties distinct from the surrounding milieu that allow for novel functions. Condensates can compartmentalize large numbers of biomolecules with related functions, thus concentrating components and accelerating biochemical reactions (Alberti et al, 2019;Banjade and Rosen, 2014;Case et al, 2019a;Huang et al, 2019;Li et al, 2012;Sheu-Gruttadauria and MacRae, 2018;Su et al, 2016;Woodruff et al, 2017;Zhang et al, 2020c). Condensates can be localized to specific sites in cells anchored, for example, by components that interact with DNA sequences or membranes (Boija et al, 2018;Case et al, 2019a;Feng et al, 2018;Huang et al, 2019;Sabari, 2020;Sabari et al, 2020;Shrinivas et al, 2019;Zeng et al, 2018).…”

Section: Biomolecular Condensatesmentioning

confidence: 99%

Biomolecular Condensates and Cancer

2021

View full text Add to dashboard Cite

“…Condensates provide potential mechanisms by which cells can rapidly regulate biochemical processes in a spatially defined manner 1,2,19,20 . Because condensates concentrate enzymes and their potential substrates, the compartments are often invoked to function by accelerating biochemical reactions.…”

Section: Introductionmentioning

confidence: 99%

Phase Separation Can Increase Enzyme Activity by Concentration and Molecular Organization

Peeples

2020

Preprint

View full text Add to dashboard Cite

Biomolecular condensates concentrate macromolecules into discrete cellular foci without an encapsulating membrane. Condensates are often presumed to increase enzymatic reaction rates through increased concentrations of enzymes and substrates (mass action), although this idea has not been widely tested and other mechanisms of modulation are possible. Here we describe a synthetic system where the SUMOylation enzyme cascade is recruited into engineered condensates generated by liquid-liquid phase separation of multidomain scaffolding proteins. SUMOylation rates can be increased up to 36-fold in these droplets compared to the surrounding bulk, depending on substrate KM. This dependency produces substantial specificity among different substrates. Analyses of reactions above and below the phase separation threshold lead to a quantitative model in which reactions in condensates are accelerated by mass action and by changes in substrate KM, likely due to scaffold-induced molecular organization. Thus, condensates can modulate reaction rates both by concentrating molecules and by physically organizing them.

show abstract

Enzymatic Reactions inside Biological Condensates

Cited by 63 publications

References 41 publications

Nuclear condensates of p300 formed though the structured catalytic core can act as a storage pool of p300 with reduced HAT activity

Nuclear condensates of p300 formed though the structured catalytic core can act as a storage pool of p300 with reduced HAT activity

Biomolecular Condensates and Cancer

Phase Separation Can Increase Enzyme Activity by Concentration and Molecular Organization

Contact Info

Product

Resources

About