protein disulfide isomerases
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Author(s):  
Evelyne Kohli ◽  
Sébastien Causse ◽  
Valentin Baverel ◽  
Laurence Dubrez ◽  
Natalia Borges-Bonan ◽  
...  

Viruses are intracellular parasites that subvert the functions of their host cells to accomplish their infection cycle. The endoplasmic reticulum (ER)-residing chaperone proteins are central for the achievement of different steps of the viral cycle, from entry and replication to assembly and exit. The most abundant ER chaperones are GRP78 (78-kDa glucose-regulated protein), GRP94 (94-kDa glucose-regulated protein), the carbohydrate or lectin-like chaperones calnexin (CNX) and calreticulin (CRT), the protein disulfide isomerases (PDIs) and the DNAJ chaperones.


2021 ◽  
Author(s):  
Bin Wang ◽  
Jing Zhang ◽  
Xin Liu ◽  
Qingqing Chai ◽  
Xiaoran Lu ◽  
...  

2020 ◽  
Author(s):  
David W. Cobb ◽  
Heather M. Kudyba ◽  
Alejandra Villegas ◽  
Michael R. Hoopmann ◽  
Rodrigo Baptista ◽  
...  

AbstractMalaria remains a major global health problem, and there exists a constant need to identify druggable weaknesses in P. falciparum biology. The endoplasmic reticulum (ER) has many essential roles in the asexual lifecycle and may offer new drug targets, but it remains critically understudied. We generated conditional mutants of the putative redox-active, ER chaperone PfJ2, and show that it is essential for parasite survival. Using a redox-active cysteine crosslinker, we identify its substrates to be other mediators of oxidative folding, PfPDI8 and PfPDI11, suggesting a redox-regulatory role for PfJ2. Knockdown of these protein disulfide isomerases in PfJ2 conditional mutants show that PfPDI11 is not essential, while PfPDI8 is essential for asexual growth and may work in a complex with PfJ2 and other ER chaperones. Finally, we show that these redox interactions in the parasite ER are sensitive to small molecule inhibition. Together these data build a model for how oxidative folding occurs in the P. falciparum ER and demonstrate its suitability for antimalarial drug development.


Aging ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 2347-2372 ◽  
Author(s):  
Zhigang Peng ◽  
Yu Chen ◽  
Hui Cao ◽  
Hecun Zou ◽  
Xin Wan ◽  
...  

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