Assessment of substrate-stabilizing factors for DnaK on the folding of aggregation-prone proteins

Ryu, Kisun; Kim, Chul Woo; Kim, Byung Hee; Han, Kyoung Sim; Kim, Kyun-Hwan; Choi, Seong Il; Seong, Baik Lin

doi:10.1016/j.bbrc.2008.05.186

Cited by 13 publications

(23 citation statements)

References 29 publications

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“…45 We showed that, in the fusion context of DnaK-aggregation prone protein, the point mutation and deletion of substrate binding domain of DnaK did not have significant impact on the cis-acting solubilizing ability of DnaK. 46 The results imply that DnaK has an intrinsic solubilizing ability to their bound substrates irrespective of its hydrophobic interaction ability. To explain how DnaK can stabilize its bound substrates also function as chaperones for protein folding.…”

Section: Discussionmentioning

confidence: 93%

RNA-mediated chaperone type for de novo protein folding

Choi¹,

Ryu²,

Seong³

2009

RNA Biology

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Section: Discussionmentioning

confidence: 93%

RNA-mediated chaperone type for de novo protein folding

Choi¹,

Ryu²,

Seong³

2009

RNA Biology

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“…However, this important assumption underlying the action mechanisms of molecular chaperones is not well demonstrated experimentally. We constructed the fusion proteins in which DnaK is linked to the N -termini of aggregation-prone proteins to mimic the DnaK-substrate complex and expressed them in the E. coli cytosol [107]. In the fusion context, the residue or domain of DnaK crucial for its substrate recognition can be changed or deleted while maintaining the complex.…”

Section: Charge and Steric Hindrance As Stabilizing Factorsmentioning

confidence: 99%

“…Neither mutation of the crucial residue nor deletion of the whole substrate-binding domain has appreciable effect on the solubilizing ability of DnaK. These findings suggest that DnaK could have its intrinsic ability to stabilize its bound substrate proteins, independent of its hydrophobic interactions with substrate proteins [107]. …”

Section: Charge and Steric Hindrance As Stabilizing Factorsmentioning

confidence: 99%

Macromolecule-Assisted de novo Protein Folding

Choi

Son

Lim

et al. 2012

IJMS

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In the processes of protein synthesis and folding, newly synthesized polypeptides are tightly connected to the macromolecules, such as ribosomes, lipid bilayers, or cotranslationally folded domains in multidomain proteins, representing a hallmark of de novo protein folding environments in vivo. Such linkage effects on the aggregation of endogenous polypeptides have been largely neglected, although all these macromolecules have been known to effectively and robustly solubilize their linked heterologous proteins in fusion or display technology. Thus, their roles in the aggregation of linked endogenous polypeptides need to be elucidated and incorporated into the mechanisms of de novo protein folding in vivo. In the classic hydrophobic interaction-based stabilizing mechanism underlying the molecular chaperone-assisted protein folding, it has been assumed that the macromolecules connected through a simple linkage without hydrophobic interactions and conformational changes would make no effect on the aggregation of their linked polypeptide chains. However, an increasing line of evidence indicates that the intrinsic properties of soluble macromolecules, especially their surface charges and excluded volume, could be important and universal factors for stabilizing their linked polypeptides against aggregation. Taken together, these macromolecules could act as folding helpers by keeping their linked nascent chains in a folding-competent state. The folding assistance provided by these macromolecules in the linkage context would give new insights into de novo protein folding inside the cell.

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“…To address this issue, the aggregation-prone proteins were fused to the C -termini of DnaK and its variants with a point mutation in the residue critical for the substrate recognition or deletion of the C -terminal substrate-binding domain [58]. Here, the assumption was that the covalent linkage can mimic the noncovalent association between DnaK and its substrate.…”

Section: Macromolecule-mediated Chaperone Type Based On Their Surfacementioning

confidence: 99%

“…The hatched area represents the surfaces inaccessible to other B by the steric masking of the corresponding A . (Adapted from Reference [58]).…”

Section: Figurementioning

confidence: 99%

Chaperoning Roles of Macromolecules Interacting with Proteins in Vivo

Choi

Lim

Seong

2011

IJMS

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The principles obtained from studies on molecular chaperones have provided explanations for the assisted protein folding in vivo. However, the majority of proteins can fold without the assistance of the known molecular chaperones, and little attention has been paid to the potential chaperoning roles of other macromolecules. During protein biogenesis and folding, newly synthesized polypeptide chains interact with a variety of macromolecules, including ribosomes, RNAs, cytoskeleton, lipid bilayer, proteolytic system, etc. In general, the hydrophobic interactions between molecular chaperones and their substrates have been widely believed to be mainly responsible for the substrate stabilization against aggregation. Emerging evidence now indicates that other features of macromolecules such as their surface charges, probably resulting in electrostatic repulsions, and steric hindrance, could play a key role in the stabilization of their linked proteins against aggregation. Such stabilizing mechanisms are expected to give new insights into our understanding of the chaperoning functions for de novo protein folding. In this review, we will discuss the possible chaperoning roles of these macromolecules in de novo folding, based on their charge and steric features.

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Assessment of substrate-stabilizing factors for DnaK on the folding of aggregation-prone proteins

Cited by 13 publications

References 29 publications

RNA-mediated chaperone type for de novo protein folding

RNA-mediated chaperone type for de novo protein folding

Macromolecule-Assisted de novo Protein Folding

Chaperoning Roles of Macromolecules Interacting with Proteins in Vivo

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