Sequestration of Proteins in Stress Granules Relies on the In-Cell but Not the In Vitro Folding Stability

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388955%3A_____%2F21%3A00548178" target="_blank" >RIV/61388955:_____/21:00548178 - isvavai.cz</a>

Výsledek na webu

<a href="http://hdl.handle.net/11104/0324283" target="_blank" >http://hdl.handle.net/11104/0324283</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/jacs.1c09589" target="_blank" >10.1021/jacs.1c09589</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Sequestration of Proteins in Stress Granules Relies on the In-Cell but Not the In Vitro Folding Stability

Popis výsledku v původním jazyce

Stress granules (SGs) are among the most studied membraneless organelles that form upon heat stress (HS) to sequester unfolded, misfolded, or aggregated protein, supporting protein quality control (PQC) clearance. The folding states that are primarily associated with SGs, as well as the function of the phase separated environment in adjusting the energy landscapes, remain unknown. Here, we investigate the association of superoxide dismutase 1 (SOD1) proteins with different folding stabilities and aggregation propensities with condensates in cells, in vitro and by simulation. We find that irrespective of aggregation the folding stability determines the association of SOD1 with SGs in cells. In vitro and in silico experiments however suggest that the increased flexibility of the unfolded state constitutes only a minor driving force to associate with the dynamic biomolecular network of the condensate. Specific protein–protein interactions in the cytoplasm in comparison to SGs determine the partitioning of folding states between the respective phases during HS.

Název v anglickém jazyce

Sequestration of Proteins in Stress Granules Relies on the In-Cell but Not the In Vitro Folding Stability

Popis výsledku anglicky

Stress granules (SGs) are among the most studied membraneless organelles that form upon heat stress (HS) to sequester unfolded, misfolded, or aggregated protein, supporting protein quality control (PQC) clearance. The folding states that are primarily associated with SGs, as well as the function of the phase separated environment in adjusting the energy landscapes, remain unknown. Here, we investigate the association of superoxide dismutase 1 (SOD1) proteins with different folding stabilities and aggregation propensities with condensates in cells, in vitro and by simulation. We find that irrespective of aggregation the folding stability determines the association of SOD1 with SGs in cells. In vitro and in silico experiments however suggest that the increased flexibility of the unfolded state constitutes only a minor driving force to associate with the dynamic biomolecular network of the condensate. Specific protein–protein interactions in the cytoplasm in comparison to SGs determine the partitioning of folding states between the respective phases during HS.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10403 - Physical chemistry

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2021

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of the American Chemical Society

ISSN

0002-7863

e-ISSN

1520-5126

Svazek periodika

143

Číslo periodika v rámci svazku

47

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

10

Strana od-do

19909-19918

Kód UT WoS článku

000750622600027

EID výsledku v databázi Scopus

2-s2.0-85119911776