Limits...
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.

Show MeSH
A model for RNA binding-mediated protein folding. Both the folded RNA-binding domain (RBD) at the N-terminal position and bound RNA prevent inter-molecular interactions among folding intermediates, leading to soluble expression and favoring kinetic network into productive folding. The number of black bars (/ and //) represents the extent of aggregation inhibition. (Reproduced from Reference [67]).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f3-ijms-12-01979: A model for RNA binding-mediated protein folding. Both the folded RNA-binding domain (RBD) at the N-terminal position and bound RNA prevent inter-molecular interactions among folding intermediates, leading to soluble expression and favoring kinetic network into productive folding. The number of black bars (/ and //) represents the extent of aggregation inhibition. (Reproduced from Reference [67]).

Mentions: We previously showed that large RNAs can increase the solubility and folding of their linked proteins, as shown in Figure 3 [67]. When an RNA-binding domain (RBD) is used as a soluble carrier, the RNA binding to RBD (RNP complex) further promoted the solubility of whole proteins and the proper folding of C-terminal proteins. The similarity between the RNP-linked aggregation-prone proteins and the ribosome-linked nascent chains made us speculate that ribosomes might contribute to the solubility enhancement of their linked nascent chains in a cis-acting manner. Indeed, the ribosome displays technology has been known to be very effective for promoting the solubility and folding of highly aggregation-prone proteins [68,69]. By combining these observations with the model in Figure 2, we proposed that the aggregation-prone nascent chains on ribosomes might gain aggregation-resistance due to the gigantic size and overall negative surface charges of ribosomes [70]. This cis-acting chaperoning role of ribosomes has the potential to alleviate the aggregation problems of nascent chains on them. In addition, the three-dimensional organization of bacterial polysomes showed that the polypeptide exit sites are positioned to maximize the distance between them for reducing intermolecular interactions of nascent chains [71]. Thus, the aggregation problems of nascent chains on ribosomes should be understood in the ribosome linkage context.


Chaperoning roles of macromolecules interacting with proteins in vivo.

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

A model for RNA binding-mediated protein folding. Both the folded RNA-binding domain (RBD) at the N-terminal position and bound RNA prevent inter-molecular interactions among folding intermediates, leading to soluble expression and favoring kinetic network into productive folding. The number of black bars (/ and //) represents the extent of aggregation inhibition. (Reproduced from Reference [67]).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f3-ijms-12-01979: A model for RNA binding-mediated protein folding. Both the folded RNA-binding domain (RBD) at the N-terminal position and bound RNA prevent inter-molecular interactions among folding intermediates, leading to soluble expression and favoring kinetic network into productive folding. The number of black bars (/ and //) represents the extent of aggregation inhibition. (Reproduced from Reference [67]).
Mentions: We previously showed that large RNAs can increase the solubility and folding of their linked proteins, as shown in Figure 3 [67]. When an RNA-binding domain (RBD) is used as a soluble carrier, the RNA binding to RBD (RNP complex) further promoted the solubility of whole proteins and the proper folding of C-terminal proteins. The similarity between the RNP-linked aggregation-prone proteins and the ribosome-linked nascent chains made us speculate that ribosomes might contribute to the solubility enhancement of their linked nascent chains in a cis-acting manner. Indeed, the ribosome displays technology has been known to be very effective for promoting the solubility and folding of highly aggregation-prone proteins [68,69]. By combining these observations with the model in Figure 2, we proposed that the aggregation-prone nascent chains on ribosomes might gain aggregation-resistance due to the gigantic size and overall negative surface charges of ribosomes [70]. This cis-acting chaperoning role of ribosomes has the potential to alleviate the aggregation problems of nascent chains on them. In addition, the three-dimensional organization of bacterial polysomes showed that the polypeptide exit sites are positioned to maximize the distance between them for reducing intermolecular interactions of nascent chains [71]. Thus, the aggregation problems of nascent chains on ribosomes should be understood in the ribosome linkage context.

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