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Chaperoning roles of macromolecules interacting with proteins in vivo.

Choi SI, Lim KH, Seong BL - Int J Mol Sci (2011)

Bottom Line: During protein biogenesis and folding, newly synthesized polypeptide chains interact with a variety of macromolecules, including ribosomes, RNAs, cytoskeleton, lipid bilayer, proteolytic system, etc.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.

View Article: PubMed Central - PubMed

Affiliation: Translational Research Center for Protein Function Control, Yonsei University, Seoul 120-749, Korea.

ABSTRACT
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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A schematic illustration of substrate-stabilizing factors of macromolecules and their correlation with the size of the macromolecule. Here, an example of a soluble macromolecule, DnaK, with varying radius r and constant surface charge density and its bound aggregation-prone protein are represented as sphere A and B, respectively. The potential factors of sphere A such as electrostatic repulsions, steric hindrance, and hydrophobic shielding are considered as a function of the radius r of sphere A. The hatched area represents the surfaces inaccessible to other B by the steric masking of the corresponding A. (Adapted from Reference [58]).
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f2-ijms-12-01979: A schematic illustration of substrate-stabilizing factors of macromolecules and their correlation with the size of the macromolecule. Here, an example of a soluble macromolecule, DnaK, with varying radius r and constant surface charge density and its bound aggregation-prone protein are represented as sphere A and B, respectively. The potential factors of sphere A such as electrostatic repulsions, steric hindrance, and hydrophobic shielding are considered as a function of the radius r of sphere A. The hatched area represents the surfaces inaccessible to other B by the steric masking of the corresponding A. (Adapted from Reference [58]).

Mentions: Would DnaK have an intrinsic and additional stabilizing ability to substrate proteins irrespective of its hydrophobic interactions with substrates? 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. There was no significant difference in the cis-acting solubilizing ability between DnaK and its variants in vivo, indicating that DnaK has an intrinsic substrate-stabilizing ability, irrespective of its hydrophobic masking by direct contacts. Based on these results, we proposed a simplified model to explain what factors of macromolecules, including DnaK, can stabilize their linked substrates (Figure 2). In this oversimplified model, a soluble macromolecule (sphere A) with varying radius (r) but constant surface charge density is associated with an aggregation-prone protein (sphere B) via limited hydrophobic contact. As radius (r) of sphere A increases, its surface net charge (related to electrostatic repulsion) and excluded volume (related to steric hindrance) are proportional to r2 and r3, respectively, whereas the hydrophobic contact area is constant. This suggests that both surface charges and steric hindrance of large soluble macromolecules, including chaperones, would provide dominant stabilizing factors as relative to hydrophobic interactions. An important implication of this model is that soluble macromolecules could have the intrinsic ability to stabilize their linked aggregation-prone polypeptide chains against aggregation, independent of the nature of linkage between them.


Chaperoning roles of macromolecules interacting with proteins in vivo.

Choi SI, Lim KH, Seong BL - Int J Mol Sci (2011)

A schematic illustration of substrate-stabilizing factors of macromolecules and their correlation with the size of the macromolecule. Here, an example of a soluble macromolecule, DnaK, with varying radius r and constant surface charge density and its bound aggregation-prone protein are represented as sphere A and B, respectively. The potential factors of sphere A such as electrostatic repulsions, steric hindrance, and hydrophobic shielding are considered as a function of the radius r of sphere A. The hatched area represents the surfaces inaccessible to other B by the steric masking of the corresponding A. (Adapted from Reference [58]).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3111645&req=5

f2-ijms-12-01979: A schematic illustration of substrate-stabilizing factors of macromolecules and their correlation with the size of the macromolecule. Here, an example of a soluble macromolecule, DnaK, with varying radius r and constant surface charge density and its bound aggregation-prone protein are represented as sphere A and B, respectively. The potential factors of sphere A such as electrostatic repulsions, steric hindrance, and hydrophobic shielding are considered as a function of the radius r of sphere A. The hatched area represents the surfaces inaccessible to other B by the steric masking of the corresponding A. (Adapted from Reference [58]).
Mentions: Would DnaK have an intrinsic and additional stabilizing ability to substrate proteins irrespective of its hydrophobic interactions with substrates? 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. There was no significant difference in the cis-acting solubilizing ability between DnaK and its variants in vivo, indicating that DnaK has an intrinsic substrate-stabilizing ability, irrespective of its hydrophobic masking by direct contacts. Based on these results, we proposed a simplified model to explain what factors of macromolecules, including DnaK, can stabilize their linked substrates (Figure 2). In this oversimplified model, a soluble macromolecule (sphere A) with varying radius (r) but constant surface charge density is associated with an aggregation-prone protein (sphere B) via limited hydrophobic contact. As radius (r) of sphere A increases, its surface net charge (related to electrostatic repulsion) and excluded volume (related to steric hindrance) are proportional to r2 and r3, respectively, whereas the hydrophobic contact area is constant. This suggests that both surface charges and steric hindrance of large soluble macromolecules, including chaperones, would provide dominant stabilizing factors as relative to hydrophobic interactions. An important implication of this model is that soluble macromolecules could have the intrinsic ability to stabilize their linked aggregation-prone polypeptide chains against aggregation, independent of the nature of linkage between them.

Bottom Line: During protein biogenesis and folding, newly synthesized polypeptide chains interact with a variety of macromolecules, including ribosomes, RNAs, cytoskeleton, lipid bilayer, proteolytic system, etc.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.

View Article: PubMed Central - PubMed

Affiliation: Translational Research Center for Protein Function Control, Yonsei University, Seoul 120-749, Korea.

ABSTRACT
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.

Show MeSH