Structural and functional dissection of reovirus capsid folding and assembly by the prefoldin-TRiC/CCT chaperone network

Knowlton, Jonathan J.; Gestaut, Daniel R.; Ma, Boxue; Taylor, Gwen M.; Seven, Alpay B.; Leitner, Alexander; Wilson, Gregory J.; Shanker, Sreejesh; Yates, Nathan A.; Prasad, B. V. Venkataram; Aebersold, Ruedi; Chiu, Wah; Frydman, Judith; Dermody, Terence S.

doi:10.1073/pnas.2018127118

Cited by 35 publications

(37 citation statements)

References 46 publications

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“…Prefoldin subunits were found to promote some viral infections. The co-chaperone function of the prefoldin complex can be utilized to accelerate the folding of reovirus capsid protein ( Knowlton et al, 2021 ). Reoviruses are rarely pathogenic in early human life but are associated with infection of the respiratory system ( Jackson and Muldoon, 1973 ) and central nervous system ( Tyler, 1998 ), gastroenteritis ( Giordano et al, 2002 ), and celiac disease ( Bouziat et al, 2017 ).…”

Section: Implications Of Prefoldin In Pathological Conditionsmentioning

confidence: 99%

“…The prefoldin complex was shown to augment the TRiC-mediated folding of σ3 reovirus capsid protein and enhance efficiency of σ3/μ1 assembly to form a heterohexameric proteinic capsid (μ1 3 σ3 3 ). In this process, PFDN2 directly interacts with reovirus σ3 protein ( Knowlton et al, 2021 ) ( Figure 6A ). Frameshift protein (F protein) of hepatitis C virus has been shown to bind to PFDN2 and impair function of the prefoldin complex.…”

Section: Implications Of Prefoldin In Pathological Conditionsmentioning

confidence: 99%

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Prefoldin Function in Cellular Protein Homeostasis and Human Diseases

Tahmaz

Ghahe

Topf

2022

Front. Cell Dev. Biol.

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Cellular functions are largely performed by proteins. Defects in the production, folding, or removal of proteins from the cell lead to perturbations in cellular functions that can result in pathological conditions for the organism. In cells, molecular chaperones are part of a network of surveillance mechanisms that maintains a functional proteome. Chaperones are involved in the folding of newly synthesized polypeptides and assist in refolding misfolded proteins and guiding proteins for degradation. The present review focuses on the molecular co-chaperone prefoldin. Its canonical function in eukaryotes involves the transfer of newly synthesized polypeptides of cytoskeletal proteins to the tailless complex polypeptide 1 ring complex (TRiC/CCT) chaperonin which assists folding of the polypeptide chain in an energy-dependent manner. The canonical function of prefoldin is well established, but recent research suggests its broader function in the maintenance of protein homeostasis under physiological and pathological conditions. Interestingly, non-canonical functions were identified for the prefoldin complex and also for its individual subunits. We discuss the latest findings on the prefoldin complex and its subunits in the regulation of transcription and proteasome-dependent protein degradation and its role in neurological diseases, cancer, viral infections and rare anomalies.

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Section: Implications Of Prefoldin In Pathological Conditionsmentioning

confidence: 99%

Section: Implications Of Prefoldin In Pathological Conditionsmentioning

confidence: 99%

Prefoldin Function in Cellular Protein Homeostasis and Human Diseases

Tahmaz

Ghahe

Topf

2022

Front. Cell Dev. Biol.

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“…X-ray crystal structures and cryo-EM structures reveal that molecular chaperones have distinct and characteristic shapes. For instance, chaperones classified as chaperonin, including GroEL in prokaryotes [ 40 ] ( Figure 3 A) and tailless complex polypeptide 1 ring complex (TRiC) (also called chaperonin containing tailless complex polypeptide 1 (CCT) in eukaryotes [ 41 ] ( Figure 3 B), are chamber-shaped; heat shock protein 90 (Hsp90) [ 42 ] ( Figure 3 C) and Hsp40 [ 43 ] are V-shaped ( Figure 3 D); SecB [ 44 ] forms a disc-shaped tetramer ( Figure 3 E); and TF [ 45 ] has elongated shape that is often represented as dragon-shape ( Figure 3 F). The structural information of chaperones provides insights into their mechanism, summarized later.…”

Section: Structural Features Of Molecular Chaperonesmentioning

confidence: 99%

Structural and Kinetic Views of Molecular Chaperones in Multidomain Protein Folding

Kawagoe

Ishimori

Saio

2022

IJMS

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Despite recent developments in protein structure prediction, the process of the structure formation, folding, remains poorly understood. Notably, folding of multidomain proteins, which involves multiple steps of segmental folding, is one of the biggest questions in protein science. Multidomain protein folding often requires the assistance of molecular chaperones. Molecular chaperones promote or delay the folding of the client protein, but the detailed mechanisms are still unclear. This review summarizes the findings of biophysical and structural studies on the mechanism of multidomain protein folding mediated by molecular chaperones and explains how molecular chaperones recognize the client proteins and alter their folding properties. Furthermore, we introduce several recent studies that describe the concept of kinetics–activity relationships to explain the mechanism of functional diversity of molecular chaperones.

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“…Following intraparticle dsRNA synthesis, the outer shell proteins are assembled onto the particle for subsequent release from infected cells. Surprisingly, with the exception of the TRiC chaperonin complex, which aids in reovirus outer shell assembly [ 25 , 26 ], few other host factors that act after ISVP formation have been identified.…”

Section: Introductionmentioning

confidence: 99%

A CRISPR-Cas9 screen reveals a role for WD repeat-containing protein 81 (WDR81) in the entry of late penetrating viruses

2022

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Successful initiation of infection by many different viruses requires their uptake into the endosomal compartment. While some viruses exit this compartment early, others must reach the degradative, acidic environment of the late endosome. Mammalian orthoreovirus (reovirus) is one such late penetrating virus. To identify host factors that are important for reovirus infection, we performed a CRISPR-Cas9 knockout (KO) screen that targets over 20,000 genes in fibroblasts derived from the embryos of C57/BL6 mice. We identified seven genes (WDR81, WDR91, RAB7, CCZ1, CTSL, GNPTAB, and SLC35A1) that were required for the induction of cell death by reovirus. Notably, CRISPR-mediated KO of WD repeat-containing protein 81 (WDR81) rendered cells resistant to reovirus infection. Susceptibility to reovirus infection was restored by complementing KO cells with human WDR81. Although the absence of WDR81 did not affect viral attachment efficiency or uptake into the endosomal compartments for initial disassembly, it reduced viral gene expression and diminished infectious virus production. Consistent with the role of WDR81 in impacting the maturation of endosomes, WDR81-deficiency led to the accumulation of reovirus particles in dead-end compartments. Though WDR81 was dispensable for infection by VSV (vesicular stomatitis virus), which exits the endosomal system at an early stage, it was required for VSV-EBO GP (VSV that expresses the Ebolavirus glycoprotein), which must reach the late endosome to initiate infection. These results reveal a previously unappreciated role for WDR81 in promoting the replication of viruses that transit through late endosomes.

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Structural and functional dissection of reovirus capsid folding and assembly by the prefoldin-TRiC/CCT chaperone network

Cited by 35 publications

References 46 publications

Prefoldin Function in Cellular Protein Homeostasis and Human Diseases

Prefoldin Function in Cellular Protein Homeostasis and Human Diseases

Structural and Kinetic Views of Molecular Chaperones in Multidomain Protein Folding

A CRISPR-Cas9 screen reveals a role for WD repeat-containing protein 81 (WDR81) in the entry of late penetrating viruses

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