‘Chaperone’ Definition
Termin ‘chaperones’ refers to the unique group of proteins that play a crucial role in our organisms. Their main activity is linked to the controlling folding processes of the other proteins after the translation on ribosomes. It is possible to consider chaperones as a type of enzymes, which is another group of proteins, and it would not be entirely incorrect due to the presence of cofactors and domains that react with substrates. However, chaperones are more versatile in their interactions with different proteins-substrates than enzymes. In other words, chaperones can easily deform, trying to adjust to more potential substrates, by changing their change [2].
Well-known chaperones, such as Hsp60, Hsp70, Hsp90 and Hsp100, which alsorequire ATP to perform their functions. These chaperones are often referred to as ‘heat shock proteins’, as reflected in their abbreviation [2].
The Chaperone’s Structure
The general structure of chaperons can be explored by examining the figure below.
Figure 1. The chaperone (Hsp70) structure.
From Figure 1, we can infer that chaperones generally consist of two domains: the nucleotide-binding domain on the N-terminal, which binds ATP, and the substrate-binding domain on the C-terminal, which binds proteins. These two sites are bounded by a linkage which allows them to change the shape of a chaperone and adhere to substrates easily. Additionally, chaperones have a lid.
Mechanism of Chaperone Function
The function of chaperones involves ATP binding, domain interactions, and hydrolysis.
First, ATP binds to the chaperone, resulting in the lid opening, and its substrate-binding domains getting close to the nucleotide-binding domain. Therefore, the fissure of a chaperone becomes smaller and closes after the substrate comes in, which provokes the linker’s site to be formed. That, in turn, makes the approximated domains bond with sites of the nucleotide-binding domain [2].
Then, the hydrolysis is provided, and the chaperone gets reactivated after work by domains distancing from each other. At the end of the process, a folded protein comes out of the chaperone, the lid closes, and the process repeats if there is another stress factor [2].
Fundamental Functions of the Chaperones and Oxidative Stress
As mentioned earlier, chaperones are involved in the protein folding process. However, they not only fold the proteins in the right way, but limit the proteins to be unfolded or folded in a wrong way, also they are able to fold back the proteins, which were partially unfolded, and decompose the protein aggregates [3].
These protein issues can arise due to internal and external factors such as stress conditions, including abrupt and prolonged exposure to cold or hot temperatures, various types of radiation (e.g., ultraviolet light, X-rays, gamma rays), water deficiency, and excessive oxygen. Excess oxygen, also known as oxidative stress, can disrupt cellular homeostasis [3, 4].
Oxidative stress is characterized by a significant changes in the oxidation-reduction balance within cells. These changes lead to an abundance of strong oxidants, which harm cellular homeostasis. Some chaperones are orientated on this kind of issue, get activated, and reestablish the redox balance by reacting with the substrate’s side chains [4].
Role of Chaperones
There is no doubt that chaperones protect the organism during stress conditions. Basically, the stress factors (e.g. dehydration), human aging, neurodegenerative diseases, and certain metabolic disorders can disrupt the oxidation-reduction balance of cell, resulting in oxidative stress, as mentioned earlier [4]. Chaperones are designed to address such problems.
Besides this advantage, the chaperone’s findings should be used in the cancer research and treatment. Due to the significant importance of chaperones in the tumor cells, the treatment can include the control of chaperones activity. The results are the words set in stone – anticancer drugs [1,2]. Furthermore, since some chaperones are absent in eukaryotic cells, some stress-activated ones were found in pathogens. It means the new usage of chaperone drugs [4].
In conclusion, chaperones are an incredible class of proteins that can truly be considered the guardians of cellular life.
REFERENCES
[1] Saibil, H. (2013). Chaperone machines for protein folding, unfolding and disaggregation. Nature Reviews Molecular Cell Biology, 14(10), 630–642. https://doi.org/10.1038/nrm3658
[2] Storey, J. M., & Storey, K. B. (2022). Chaperone proteins: universal roles in surviving environmental stress. Cell Stress and Chaperones, 28(5), 455–466. https://doi.org/10.1007/s12192-022-01312-x
[3] Voth, W., & Jakob, U. (2017). Stress-Activated chaperones: a first line of defense. Trends in Biochemical Sciences, 42(11), 899–913. https://doi.org/10.1016/j.tibs.2017.08.006
[4] Buchner, J. (2019). Molecular chaperones and protein quality control: an introduction to the JBC Reviews thematic series. Journal of Biological Chemistry, 294(6), 2074–2075. https://doi.org/10.1074/jbc.rev118.006739
Figures
Figure 1. Structure of Hsp70. Adapted from: International Journal of Molecular Sciences, 25(8), Article 876. https://doi.org/10.3390/ijms2508076
