Protein Quality Control Through Molecular Chaperones, Protein Folding Catalysts and ATP-dependent Proteases

2006 ◽  
pp. 271-307
Keyword(s):  
Quality Control ◽  
Protein Folding ◽  
Molecular Chaperones ◽  
Protein Quality ◽  
Protein Quality Control

scholarly journals Molecular chaperones and stress-inducible protein-sorting factors coordinate the spatiotemporal distribution of protein aggregates

2012 ◽  
Vol 23 (16) ◽  
pp. 3041-3056 ◽  
Author(s):  
Liliana Malinovska ◽  
Sonja Kroschwald ◽  
Matthias C. Munder ◽  
Doris Richter ◽  
Simon Alberti
Keyword(s):  
Quality Control ◽  
Molecular Chaperones ◽  
Cellular Response ◽  
Protein Quality ◽  
Acute Stress ◽  
Protein Sorting ◽  
Protein Quality Control ◽  
Normal Growth ◽  
Small Heat Shock Protein ◽  
Misfolded Proteins

Acute stress causes a rapid redistribution of protein quality control components and aggregation-prone proteins to diverse subcellular compartments. How these remarkable changes come about is not well understood. Using a phenotypic reporter for a synthetic yeast prion, we identified two protein-sorting factors of the Hook family, termed Btn2 and Cur1, as key regulators of spatial protein quality control in Saccharomyces cerevisiae. Btn2 and Cur1 are undetectable under normal growth conditions but accumulate in stressed cells due to increased gene expression and reduced proteasomal turnover. Newly synthesized Btn2 can associate with the small heat shock protein Hsp42 to promote the sorting of misfolded proteins to a peripheral protein deposition site. Alternatively, Btn2 can bind to the chaperone Sis1 to facilitate the targeting of misfolded proteins to a juxtanuclear compartment. Protein redistribution by Btn2 is accompanied by a gradual depletion of Sis1 from the cytosol, which is mediated by the sorting factor Cur1. On the basis of these findings, we propose a dynamic model that explains the subcellular distribution of misfolded proteins as a function of the cytosolic concentrations of molecular chaperones and protein-sorting factors. Our model suggests that protein aggregation is not a haphazard process but rather an orchestrated cellular response that adjusts the flux of misfolded proteins to the capacities of the protein quality control system.

scholarly journals An Hsp90 co-chaperone links protein folding and degradation and is part of a conserved protein quality control

Cell Reports ◽  
2021 ◽  
Vol 35 (13) ◽  
pp. 109328
Author(s):  
Frederik Eisele ◽  
Anna Maria Eisele-Bürger ◽  
Xinxin Hao ◽  
Lisa Larsson Berglund ◽  
Johanna L. Höög ◽  
...  
Keyword(s):  
Quality Control ◽  
Protein Folding ◽  
Protein Quality ◽  
Protein Quality Control

scholarly journals Molecular Chaperones in Protein Quality Control

BMB Reports ◽  
2005 ◽  
Vol 38 (3) ◽  
pp. 259-265 ◽  
Author(s):  
Suk-Yeong Lee ◽  
Francis T.F. Tsai
Keyword(s):  
Quality Control ◽  
Molecular Chaperones ◽  
Protein Quality ◽  
Protein Quality Control

scholarly journals Clearing Traffic Jams During Protein Translocation Across Membranes

2021 ◽  
Vol 8 ◽  
Author(s):  
Lihui Wang ◽  
Yihong Ye
Keyword(s):  
Quality Control ◽  
Endoplasmic Reticulum ◽  
Protein Folding ◽  
Lipid Bilayers ◽  
Protein Quality ◽  
Protein Translocation ◽  
Control Strategies ◽  
Protein Quality Control ◽  
Traffic Jams ◽  
Protein Biogenesis

Protein translocation across membranes is a critical facet of protein biogenesis in compartmentalized cells as proteins synthesized in the cytoplasm often need to traverse across lipid bilayers via proteinaceous channels to reach their final destinations. It is well established that protein biogenesis is tightly linked to various protein quality control processes, which monitor errors in protein folding, modification, and localization. However, little is known about how cells cope with translocation defective polypeptides that clog translocation channels (translocons) during protein translocation. This review summarizes recent studies, which collectively reveal a set of translocon-associated quality control strategies for eliminating polypeptides stuck in protein-conducting channels in the endoplasmic reticulum and mitochondria.

scholarly journals Structural basis of DegP-protease temperature-dependent activation

2020 ◽  
Author(s):  
Darius Šulskis ◽  
Johannes Thoma ◽  
Björn M. Burmann
Keyword(s):  
Quality Control ◽  
Molecular Chaperones ◽  
Protein Quality ◽  
Protein Quality Control ◽  
Structural Basis ◽  
Pdz Domains ◽  
Unfolded Proteins ◽  
Temperature Dependent ◽  
E Coli ◽  
High Resolution Nmr

AbstractProtein quality control is an essential cellular function and it is mainly executed by a large array of proteases and molecular chaperones. One of the bacterial HtrA protein family members, the homo-oligomeric DegP-protease, plays a crucial role in the Escherichia coli (E. coli) protein quality control machinery by removing unfolded proteins or preventing them from aggregation and chaperoning them until they are properly folded within the periplasm. DegP contains two regulatory PDZ domains, which play key roles in substrate recognition as well as in the transformation of DegP to proteolytic cage-like structures. Here, we analyse the interaction and dynamics of the PDZ-domains of DegP underlying this transformation in solution by high-resolution NMR spectroscopy. We identify an interdomain molecular lock guiding the interactions between both PDZ domains, regulated by fine-tuned protein dynamics and potentially conserved in proteins harboring tandem PDZ domains.

scholarly journals The Degradation-promoting Roles of Deubiquitinases Ubp6 and Ubp3 in Cytosolic and ER Protein Quality Control

2020 ◽  
Author(s):  
Hongyi Wu ◽  
Davis T.W. Ng ◽  
Ian Cheong ◽  
Paul Matsudaira
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Quality Control ◽  
Molecular Chaperones ◽  
Protein Quality ◽  
Protein Quality Control ◽  
Ubiquitin Proteasome System ◽  
Misfolded Proteins ◽  
Intracellular Proteins ◽  
Ubiquitin Proteasome ◽  
Free Ubiquitin

AbstractThe quality control of intracellular proteins is achieved by degrading misfolded proteins which cannot be refolded by molecular chaperones. In eukaryotes, such degradation is handled primarily by the ubiquitin-proteasome system. However, it remains unclear whether and how protein quality control deploys various deubiquitinases. To address this question, we screened deletions or mutation of the 20 deubiquitinase genes in Saccharomyces cerevisiae and discovered that almost half of the mutations slowed the removal of misfolded proteins whereas none of the remaining mutations accelerated this process significantly. Further characterization revealed that Ubp6 maintains the level of free ubiquitin to promote the elimination of misfolded cytosolic proteins, while Ubp3 supports the degradation of misfolded cytosolic and ER luminal proteins by different mechanisms.

scholarly journals Protein quality control in the secretory pathway

2019 ◽  
Vol 218 (10) ◽  
pp. 3171-3187 ◽  
Author(s):  
Zhihao Sun ◽  
Jeffrey L. Brodsky
Keyword(s):  
Quality Control ◽  
Protein Folding ◽  
Secretory Pathway ◽  
Protein Quality ◽  
Protein Quality Control ◽  
Misfolded Proteins ◽  
Unfolded Protein ◽  
Protein Biogenesis ◽  
The Unfolded Protein Response ◽  
Protein Response

Protein folding is inherently error prone, especially in the endoplasmic reticulum (ER). Even with an elaborate network of molecular chaperones and protein folding facilitators, misfolding can occur quite frequently. To maintain protein homeostasis, eukaryotes have evolved a series of protein quality-control checkpoints. When secretory pathway quality-control pathways fail, stress response pathways, such as the unfolded protein response (UPR), are induced. In addition, the ER, which is the initial hub of protein biogenesis in the secretory pathway, triages misfolded proteins by delivering substrates to the proteasome or to the lysosome/vacuole through ER-associated degradation (ERAD) or ER-phagy. Some misfolded proteins escape the ER and are instead selected for Golgi quality control. These substrates are targeted for degradation after retrieval to the ER or delivery to the lysosome/vacuole. Here, we discuss how these guardian pathways function, how their activities intersect upon induction of the UPR, and how decisions are made to dispose of misfolded proteins in the secretory pathway.

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