Investigation on different chemical stability of mitochondrial Hsp60 and its precursor

Ricci, Caterina; Carrotta, Rita; Rappa, Giacoma Cinzia; Mangione, Maria Rosalia; Librizzi, Fabio; Biagio, Pier Luigi San; Amenitsch, Heinz; Ortore, María Grazia; Vilasi, Silvia

doi:10.1016/j.bpc.2017.07.008

Cited by 8 publications

(12 citation statements)

References 38 publications

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“…22 Mitochondrial import segment also aids in naive HSP60 stabilization and makes it more resistant to denaturant conditions, properties that are lost in mtHSP60, however said resulting instability seems to be important for its physiologic role in the mitochondria. 22 Nonetheless, as naive HSP60 in aqueous solution, a study has demonstrated that its structure can be found in stable heptamers and tetradecamers at different concentrations. 23 In its minimal functional unit, HSP60 exists as a single ring structure forming a heptameric toroid, although it is mostly present as two-stacked heptameric rings which form a central enclosure where proteins are folded in an ATPase-dependent activity.…”

Section: Structural Characteristicsmentioning

confidence: 99%

Heat shock protein 60 and cardiovascular diseases: An intricate love‐hate story

Krishnan-Sivadoss

Mijares-Rojas

Villarreal-Leal

et al. 2020

Medicinal Research Reviews

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Cardiovascular diseases (CVDs) are the result of complex pathophysiological processes in the tissues comprising the heart and blood vessels. Inflammation is the main culprit for the development of cardiovascular dysfunction, and it may be traced to cellular stress events including apoptosis, oxidative and shear stress, and cellular and humoral immune responses, all of which impair the system's structure and function. An intracellular chaperone, heat shock protein 60 (HSP60) is an intriguing example of a protein that may both be an ally and a foe for cardiovascular homeostasis; on one hand providing protection against cellular injury, and on the other triggering damaging responses through innate and adaptive immunity. In this review we will discuss the functions of HSP60 and its effects on cells and the immune system regulation, only to later address its implications in the development and progression of CVD. Lastly, we summarize the outcome of various studies targeting HSP60 as a potential therapeutic strategy for cardiovascular and other diseases.

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Section: Structural Characteristicsmentioning

confidence: 99%

Heat shock protein 60 and cardiovascular diseases: An intricate love‐hate story

Krishnan-Sivadoss

Mijares-Rojas

Villarreal-Leal

et al. 2020

Medicinal Research Reviews

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“…When the Hsp60 N-terminus is analyzed by PONDR VLXT, a neural networks disorder predictor, it appears that in the absence of MTS, residues adjacent to it undergo an order-disorder transition, probably related to the functional role that the chaperonin plays in mitochondria (Ricci et al, 2017 ).…”

Section: Hsp60 Outside Mitochondriamentioning

confidence: 99%

“…For instance, it has been demonstrated that a single mutation in HSP60 found in MitCHAP-60 destabilizes the chaperonin oligomers (Parnas et al, 2009 ). This is why in view of the potentially key roles of naïve HSP60 in cancer and other diseases, several studies have focused on its oligomeric organization and structure (Vilasi et al, 2014 ; Ricci et al, 2016 , 2017 ; Enriquez et al, 2017 ). A detailed study of the structure and self-organization of naïve cytosolic recombinant His-tag HSP60 in solution was performed, using biophysical methods such as Light and X-Ray Scattering, Single Molecule Spectroscopy, and hydrodynamics measurements (Vilasi et al, 2014 ).…”

Section: Hsp60 Outside Mitochondriamentioning

confidence: 99%

“…It is worth noting that mature HSP60 produced without His6-tag occurs predominantly as single rings (Nielsen and Cowan, 1998 ; Parnas et al, 2009 ), whereas for naïve HSP60 the equilibrium seems to shift toward double rings. Structural differences between the two HSP60 forms can also be inferred from the studies on the chemical stability of the two proteins, (Figure 6 ) (Ricci et al, 2016 , 2017 ). In order to corroborate this suggestion, further studies are needed to directly compare the two proteins, possibly purified under the same conditions, also in relation to their different activity.…”

Section: Hsp60 Outside Mitochondriamentioning

confidence: 99%

“…The free energy was calculated from the denaturation profile induced by guanidine hydrochloride evaluated by Circular Dichroism (CD) (dark gray) and Small X-Ray Angle Scattering (SAXS) (light gray). Details on data analysis are reported in Ricci et al ( 2016 , 2017 ). GroEL appears more stable than human chaperonins and mitochondrial mature HSP60 less stable than naïve HSP60.…”

Section: Hsp60 Outside Mitochondriamentioning

confidence: 99%

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

Vilasi

Bulone

Bavisotto

et al. 2018

Front. Mol. Biosci.

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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.

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