From Levinthal's Paradox to the Effects of Cell Environmental Perturbation on Protein Folding.
Protein folding
crowded cell-like environment
environmental temperature
free energy landscape
glycosylation and acetylation
phosphorylation.
Journal
Current medicinal chemistry
ISSN: 1875-533X
Titre abrégé: Curr Med Chem
Pays: United Arab Emirates
ID NLM: 9440157
Informations de publication
Date de publication:
2019
2019
Historique:
received:
28
03
2018
revised:
04
07
2018
accepted:
03
08
2018
pubmed:
20
10
2018
medline:
28
1
2020
entrez:
19
10
2018
Statut:
ppublish
Résumé
The rapidly increasing number of known protein sequences calls for more efficient methods to predict the Three-Dimensional (3D) structures of proteins, thus providing basic knowledge for rational drug design. Understanding the folding mechanism of proteins is valuable for predicting their 3D structures and for designing proteins with new functions and medicinal applications. Levinthal's paradox is that although the astronomical number of conformations possible even for proteins as small as 100 residues cannot be fully sampled, proteins in nature normally fold into the native state within timescales ranging from microseconds to hours. These conflicting results reveal that there are factors in organisms that can assist in protein folding. In this paper, we selected a crowded cell-like environment and temperature, and the top three Posttranslational Modifications (PTMs) as examples to show that Levinthal's paradox does not reflect the folding mechanism of proteins. We then revealed the effects of these factors on protein folding. The results summarized in this review indicate that a crowded cell-like environment, temperature, and the top three PTMs reshape the Free Energy Landscapes (FELs) of proteins, thereby regulating the folding process. The balance between entropy and enthalpy is the key to understanding the effect of the crowded cell-like environment and PTMs on protein folding. In addition, the stability/flexibility of proteins is regulated by temperature. This paper concludes that the cellular environment could directly intervene in protein folding. The long-term interactions of the cellular environment and sequence evolution may enable proteins to fold efficiently. Therefore, to correctly understand the folding mechanism of proteins, the effect of the cellular environment on protein folding should be considered.
Sections du résumé
BACKGROUND
BACKGROUND
The rapidly increasing number of known protein sequences calls for more efficient methods to predict the Three-Dimensional (3D) structures of proteins, thus providing basic knowledge for rational drug design. Understanding the folding mechanism of proteins is valuable for predicting their 3D structures and for designing proteins with new functions and medicinal applications. Levinthal's paradox is that although the astronomical number of conformations possible even for proteins as small as 100 residues cannot be fully sampled, proteins in nature normally fold into the native state within timescales ranging from microseconds to hours. These conflicting results reveal that there are factors in organisms that can assist in protein folding.
METHODS
METHODS
In this paper, we selected a crowded cell-like environment and temperature, and the top three Posttranslational Modifications (PTMs) as examples to show that Levinthal's paradox does not reflect the folding mechanism of proteins. We then revealed the effects of these factors on protein folding.
RESULTS
RESULTS
The results summarized in this review indicate that a crowded cell-like environment, temperature, and the top three PTMs reshape the Free Energy Landscapes (FELs) of proteins, thereby regulating the folding process. The balance between entropy and enthalpy is the key to understanding the effect of the crowded cell-like environment and PTMs on protein folding. In addition, the stability/flexibility of proteins is regulated by temperature.
CONCLUSION
CONCLUSIONS
This paper concludes that the cellular environment could directly intervene in protein folding. The long-term interactions of the cellular environment and sequence evolution may enable proteins to fold efficiently. Therefore, to correctly understand the folding mechanism of proteins, the effect of the cellular environment on protein folding should be considered.
Identifiants
pubmed: 30332937
pii: CMC-EPUB-93792
doi: 10.2174/0929867325666181017160857
doi:
Substances chimiques
Proteins
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
7537-7554Informations de copyright
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