Related Experiment Video
Updated: Dec 17, 2025
07:18
Intracellular Refolding Assay
Published on: January 24, 2012
14.6K
Hsp60 Post-translational Modifications: Functional and Pathological Consequences
Celeste Caruso Bavisotto1,2, Giusi Alberti1, Alessandra Maria Vitale1
1Section of Human Anatomy, Department of Biomedicine, Neuroscience and Advanced Diagnostic (BIND), University of Palermo, Palermo, Italy.
Frontiers in Molecular Biosciences
|June 26, 2020
Summary
Heat shock protein 60 (Hsp60) performs diverse functions beyond its canonical mitochondrial role, influenced by various post-translational modifications (PTMs). Understanding these PTMs is crucial for identifying pathogenic mechanisms in Hsp60 chaperonopathies.
Area of Science:
- Molecular Biology
- Cellular Biology
- Biochemistry
Background:
- Heat shock protein 60 (Hsp60) is a Group I Chaperonin primarily functioning within mitochondria to maintain protein homeostasis with Hsp10.
- Hsp60 exhibits non-canonical roles outside mitochondria, including in the cytoplasm, cell membrane, extracellular space, and bodily fluids.
- These diverse functions are critical in processes such as inflammation, autoimmunity, carcinogenesis, and cell replication in both health and disease.
Purpose of the Study:
- To investigate the mechanisms by which a single Hsp60 gene can lead to multifaceted protein functions and locations.
- To explore the role of post-translational modifications (PTMs) in diversifying Hsp60's molecular properties and cellular activities.
- To highlight the significance of PTMs in understanding Hsp60-related diseases (chaperonopathies).
Main Methods:
- Review and analysis of existing literature on Hsp60 functions and post-translational modifications.
- Identification of potential and confirmed PTMs on Hsp60, including phosphorylation, O-GlcNAcylation, nitration, acetylation, S-nitrosylation, citrullination, oxidation, and ubiquitination.
- Examination of the functional consequences of specific PTMs on Hsp60's cellular and tissue roles.
Main Results:
- Hsp60's amino acid sequence contains numerous sites for various PTMs, suggesting a significant role for modifications in its functional diversity.
- Specific PTMs like phosphorylation, nitration, acetylation, S-nitrosylation, citrullination, oxidation, and ubiquitination have been linked to distinct Hsp60 functions and cellular events.
- These modifications impact processes ranging from mitochondrial function and apoptosis to cell migration and protein stability.
Conclusions:
- Post-translational modifications are key drivers of Hsp60's multifaceted nature, enabling its diverse cellular and tissue functions.
- Further research is needed to precisely link specific PTMs to variations in Hsp60 properties and functions.
- Identifying pathogenic PTMs is crucial for understanding and potentially treating Hsp60 chaperonopathies, many of which are severe diseases.
Related Concept Videos
02:04Covalently Linked Protein Regulators
8.5K
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
These groups modify specific amino acids in a protein....
8.5K
03:00Molecular Chaperones and Protein Folding
19.3K
The native conformation of a protein is formed by interactions between the side chains of its constituent amino acids. When the amino acids cannot form these interactions, the protein cannot fold by itself and needs chaperones. Notably, chaperones do not relay any additional information required for the folding of polypeptides; the native conformation of a protein is determined solely by its amino acid sequence. Chaperones catalyze protein folding without being a part of the folded protein.
The...
The...
19.3K
01:26Bacterial Protein Maturation
346
Bacterial protein maturation is a tightly regulated process that ensures newly synthesized polypeptides achieve correct functional conformations. This maturation involves a series of modifications, folding events, and quality control steps, often assisted by specialized chaperone proteins.N-Terminal ModificationsThe maturation of bacterial polypeptides begins cotranslationally as the polypeptide exits the ribosome. The first amino acid, N-formylmethionine (fMet), is typically modified at the...
346
01:13The Proteasome
1.5K
Eukaryotic cells can degrade proteins through several pathways. One of the most important among these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
1.5K
02:18The Proteasome
9.9K
Eukaryotic cells can degrade proteins through several pathways. One of the most important amongst these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
9.9K
01:37The Unfolded Protein Response
6.1K
The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
6.1K