Localization of Prefoldin Interaction Sites in the Hyperthermophilic Group II Chaperonin and Correlations between Binding Rate and Protein Transfer Rate

Zako, Tamotsu; Murase, Y.; Iizuka, Ryo; Yoshida, Takao; Kanzaki, Taro; Ide, Naoki; Maeda, Mizuo; Funatsu, Takashi; Yohda, Masafumi

doi:10.1016/j.jmb.2006.08.088

Cited by 43 publications

(45 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…One particular family of chaperones, the prefoldins (PFDs), works in an ATP-independent manner to arrest protein misfolding and aggregation, transferring unfolded proteins to other chaperone complexes for refolding [2][3][4][5]. The PFDs are typically hetero-hexameric complexes found in both Archaea and eukaryotes, which have diverged in subunit composition, from two a and four b subunits in Archaea to six different subunits in eukaryotes.…”

Section: Introductionmentioning

confidence: 99%

Oligomeric assembly is required for chaperone activity of the filamentous γ‐prefoldin

Glover

Clark

2015

The FEBS Journal

View full text Add to dashboard Cite

Prefoldins (PFDs) are molecular chaperones with a distinctive jellyfishshape that have a general role in de novo protein folding in Archaea and in the biogenesis of cytoskeleton proteins in eukaryotes. In general, PFDs are hetero-hexameric protein assemblies consisting of two a and four b subunits. However, a PFD variant called gamma-prefoldin (cPFD), isolated from the hyperthermophilic archaeon Methanocaldococcus jannaschii, exhibits a unique filamentous structure that is composed of hundreds of monomeric subunits. In this study, we investigated the relationship between the morphology of the cPFD filament and its ability to prevent protein aggregation. A chaperone assay demonstrated that cPFD must be in a filamentous assembly for functional activity and the distal regions of the coiled-coils are required for binding of non-native proteins. Molecular dynamic simulations were used to model the interactions between in silico thermally denatured protein substrates and the coiled-coils of a cPFD filament. During molecular dynamic simulations at 300 and 353 K, each coiled-coil was highly flexible, enabling it to widen the central cavity of the filament to potentially capture various non-native proteins. Docking molecular dynamic simulations of cPFD filaments with unfolded citrate synthase or insulin showed a size-dependence between the substrate and the number of interacting coiled-coils. To confirm this observation, we generated filaments containing specific numbers of subunits, and showed that between six and eight cPFD subunits are required for chaperone activity to prevent citrate synthase from thermal aggregation. These results provide insights into structure-function relationships of oligomeric chaperones and illuminate the potential role of cPFD in its native environment.

show abstract

Section: Introductionmentioning

confidence: 99%

Oligomeric assembly is required for chaperone activity of the filamentous γ‐prefoldin

Glover

Clark

2015

The FEBS Journal

View full text Add to dashboard Cite

show abstract

“…8 Biochemical studies have shown that PFDs bind and stabilize unfolded target polypeptides and subsequently deliver them to CPNs to complete folding. [9][10][11] The transfer of a substrate from PFD to CPN involves a direct interaction. 11,12 We have studied the mechanism of protein folding mediated by the archaeal PFD-CPN system.…”

Section: Introductionmentioning

confidence: 99%

“…[9][10][11] The transfer of a substrate from PFD to CPN involves a direct interaction. 11,12 We have studied the mechanism of protein folding mediated by the archaeal PFD-CPN system. 9,10,13 PhPFD and PFDs of Thermococcus strain KS-1 (T. KS-1) can capture an acid-denatured green fluorescence protein (GFP) and transfer it to T. KS-1 CPN for ATPdependent folding.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Thermodynamic Characterization of the Interaction between Prefoldin and Group II Chaperonin

Sahlan

Zako

Tai

et al. 2010

Journal of Molecular Biology

Self Cite

View full text Add to dashboard Cite

“…Prefoldin captures a protein-folding intermediate and transfers it to a group II chaperonin for correct folding [11]. In fact, the Prefoldin acts as a transporter molecule that transports bound unfolded target proteins to the chaperonin molecule [12].…”

Section: Introductionmentioning

confidence: 99%

Cavity Control of Prefoldin Nano Actuator (PNA) by Temperature and pH

2012

View full text Add to dashboard Cite

A molecular dynamics study to investigate the cavity control of Prefoldin based bio nano actuator is presented in this paper. Prefoldin is a molecular chaperone with a jellyfish-like structure containing six long coiled-coil tentacles and a large central cavity. We took the temperature and pH of the medium into account, and analyzed the conformational flexibility of the Prefoldin nano actuator in details. Results show that the prefoldin is a very flexible protein, the conformational state of which appears to depend on the temperature and pH values of the medium. In fact, combining these two control parameters, a suitable environment is provided to capture nano cargoes with specific dimensions. These properties of Prefoldin actuator can be used for drug delivery in the body.

show abstract

Localization of Prefoldin Interaction Sites in the Hyperthermophilic Group II Chaperonin and Correlations between Binding Rate and Protein Transfer Rate

Cited by 43 publications

References 28 publications

Oligomeric assembly is required for chaperone activity of the filamentous γ‐prefoldin

Oligomeric assembly is required for chaperone activity of the filamentous γ‐prefoldin

Thermodynamic Characterization of the Interaction between Prefoldin and Group II Chaperonin

Cavity Control of Prefoldin Nano Actuator (PNA) by Temperature and pH

Contact Info

Product

Resources

About