Boosting the enzymatic activity of CxxC motif-containing PDI family members

Kuramochi, Tsubura; Yamashita, Yukino; Arai, Kenta; Kanemura, Shingo; Muraoka, Takahiro; Okumura, Masaki

doi:10.1039/d4cc01712a

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2024

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Cited by 2 publications

References 26 publications

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Redox-active chemical chaperones exhibiting promiscuous binding promote oxidative protein folding under condensed sub-millimolar conditions

Suzuki,

Nojiri,

Matsusaki

et al. 2024

Chem. Sci.

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Redox-active chemical chaperones exhibiting promiscuous binding promote oxidative protein folding under condensed sub-millimolar conditions

Suzuki,

Nojiri,

Matsusaki

et al. 2024

Chem. Sci.

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Ca²⁺-driven PDIA6 phase separation to ensure proinsulin quality control

Lee,

Saio,

Watabe

et al. 2024

Preprint

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The endoplasmic reticulum (ER) plays key roles in protein quality control and dynamic Ca2+> storage in eukaryotic cells. However, the protein homeostasis (proteostasis) system that regulates these ER functions is still incompletely characterised. Previous study revealed the importance of oligomerization in the function PDIA1, an ER-resident disulfide isomerase and molecular chaperone, regulates oligomeric states in accordance with client folding. This result suggests that at least some of the 20 members of other PDI family may undergo regulated self-assembly in order to optimally function. Here, we show that Ca2+ triggers the phase separation of PDIA6 into liquid-like condensates. In contrast to the condensation mechanism observed for proteins containing low-complexity domains, our results indicate that transient but specific electrostatic interactions occur between the first and the third folded thioredoxin-like domains of PDIA6. We further show that the Ca2+-driven condensation of PDIA6 recruits PDIA3 and proinsulin, thus increasing their local concentrations. This process results in the 30-fold enhancement of proinsulin folding and in the inhibition of proinsulin aggregation. Our findings shed light on a condensation-driven Ca2+-mediated proteostasis cascade in the ER by revealing how the efficiency of the protein folding process can be enhanced within quality control granules.

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Boosting the enzymatic activity of CxxC motif-containing PDI family members

Abstract: Compounds harboring high acidity and oxidizability of thiol groups permit tuning the redox equilibrium constants of CxxC sites of members of the protein disulphide isomerase family (PDIs) and thus can...

Cited by 2 publications

References 26 publications

Redox-active chemical chaperones exhibiting promiscuous binding promote oxidative protein folding under condensed sub-millimolar conditions

Redox-active chemical chaperones exhibiting promiscuous binding promote oxidative protein folding under condensed sub-millimolar conditions

Ca²⁺-driven PDIA6 phase separation to ensure proinsulin quality control

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Boosting the enzymatic activity of CxxC motif-containing PDI family members

Abstract: Compounds harboring high acidity and oxidizability of thiol groups permit tuning the redox equilibrium constants of CxxC sites of members of the protein disulphide isomerase family (PDIs) and thus can...

Cited by 2 publications

References 26 publications

Redox-active chemical chaperones exhibiting promiscuous binding promote oxidative protein folding under condensed sub-millimolar conditions

Redox-active chemical chaperones exhibiting promiscuous binding promote oxidative protein folding under condensed sub-millimolar conditions

Ca2+-driven PDIA6 phase separation to ensure proinsulin quality control

Contact Info

Product

Resources

About

Ca²⁺-driven PDIA6 phase separation to ensure proinsulin quality control