A high throughput substrate binding assay reveals hexachlorophene as an inhibitor of the ER-resident HSP70 chaperone GRP78
نویسندگان
چکیده
منابع مشابه
Analysis of rice ER-resident J-proteins reveals diversity and functional differentiation of the ER-resident Hsp70 system in plants
The heat shock protein 70 (Hsp70) chaperone system participates in protein folding and quality control of unfolded proteins. To examine the roles of co-chaperones in the rice Hsp70 chaperone system in the endoplasmic reticulum (ER), the functions of six ER-resident J-proteins (OsP58A, OsP58B, OsERdj2, OsERdj3A, OsERdj3B, and OsERdj7) in rice were investigated. The expression of OsP58B, OsERdj3A...
متن کاملRepositioning of Verrucosidin, a Purported Inhibitor of Chaperone Protein GRP78, as an Inhibitor of Mitochondrial Electron Transport Chain Complex I
Verrucosidin (VCD) belongs to a group of fungal metabolites that were identified in screening programs to detect molecules that preferentially kill cancer cells under glucose-deprived conditions. Its mode of action was proposed to involve inhibition of increased GRP78 (glucose regulated protein 78) expression during hypoglycemia. Because GRP78 plays an important role in tumorigenesis, inhibitor...
متن کاملA novel pathogenic role of the ER chaperone GRP78/BiP in rheumatoid arthritis
An accumulation of misfolded proteins can trigger a cellular survival response in the endoplasmic reticulum (ER). In this study, we found that ER stress-associated gene signatures were highly expressed in rheumatoid arthritis (RA) synoviums and synovial cells. Proinflammatory cytokines, such as TNF and IL-1β, increased the expression of GRP78/BiP, a representative ER chaperone, in RA synoviocyt...
متن کاملConserved conformational selection mechanism of Hsp70 chaperone-substrate interactions
Molecular recognition is integral to biological function and frequently involves preferred binding of a molecule to one of several exchanging ligand conformations in solution. In such a process the bound structure can be selected from the ensemble of interconverting ligands a priori (conformational selection, CS) or may form once the ligand is bound (induced fit, IF). Here we focus on the ubiqu...
متن کاملPromiscuous binding by Hsp70 results in conformational heterogeneity and fuzzy chaperone-substrate ensembles
The Hsp70 chaperone system is integrated into a myriad of biochemical processes that are critical for cellular proteostasis. Although detailed pictures of Hsp70 bound with peptides have emerged, correspondingly detailed structural information on complexes with folding-competent substrates remains lacking. Here we report a methyl-TROSY based solution NMR study showing that the Escherichia coli v...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
ژورنال
عنوان ژورنال: Bioorganic & Medicinal Chemistry Letters
سال: 2019
ISSN: 0960-894X
DOI: 10.1016/j.bmcl.2019.05.041