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Front Mol Biosci. 2018 Jan 25;4:99. doi: 10.3389/fmolb.2017.00099. eCollection 2017.

Chaperonin of Group I: Oligomeric Spectrum and Biochemical and Biological Implications.

Author information

1
Institute of Biophysics, National Research Council, Palermo, Italy.
2
Section of Human Anatomy, Department of Experimental Biomedicine and Clinical Neuroscience (BIONEC), University of Palermo, Palermo, Italy.
3
Euro-Mediterranean Institute of Science and Technology (IEMEST), Palermo, Italy.
4
Department of Microbiology and Immunology, School of Medicine, University of Maryland at Baltimore, and Institute of Marine and Environmental Technology (IMET), Columbus Center, Baltimore, MD, United States.

Abstract

Chaperonins play various physiological roles and can also be pathogenic. Elucidation of their structure, e.g., oligomeric status and post-translational modifications (PTM), is necessary to understand their functions and mechanisms of action in health and disease. Group I chaperonins form tetradecamers with two stacked heptameric rings. The tetradecamer is considered the typical functional complex for folding of client polypeptides. However, other forms such as the monomer and oligomers with smaller number of subunits than the classical tetradecamer, also occur in cells. The properties and functions of the monomer and oligomers, and their roles in chaperonin-associated diseases are still incompletely understood. Chaperonin I in eukaryotes occurs in various locations, not just the mitochondrion, which is its canonical place of residence and function. Eukaryotic Chaperonin I, namely Hsp60 (designated HSP60 or HSPD1 in humans) has, indeed, been found in the cytosol; the plasma-cell membrane; on the outer surface of cells; in the intercellular space; in biological liquids such as lymph, blood, and cerebrospinal fluid; and in secretions, for instance saliva and urine. Hsp60 has also been found in cell-derived vesicles such as exosomes. The functions of Hsp60 in all these non-canonical locales are still poorly characterized and one of the questions not yet answered is in what form, i.e., monomer or oligomer, is the chaperonin present in these non-canonical locations. In view of the steady increase in interest on chaperonopathies over the last several years, we have studied human HSP60 to determine its role in various diseases, its locations in cells and tissues and migrations in the body, and its post-translational modifications that might have an impact on its location and function. We also carried out experiments to characterize the oligomeric status of extramitochondrial of HSP60 in solution. Here, we provide an overview of our results, focusing on the oligomeric equilibrium and stability of the various forms of HSP60 in comparison with GroEL. We also discuss post-translational modifications associated with anti-cancer drugs to indicate the potential of Hsp60 in Medicine, as a biomarker and etiopathogenic factor.

KEYWORDS:

GroEL; Hsp60; chaperonopathies; heptamer; monomer; non-canonical locales; post-translation modification; tetradecamer

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