Bridging human chaperonopathies and microbial chaperonins

Abstract

Chaperonins are molecular chaperones that play critical physiological roles, but they can be pathogenic. Malfunctional chaperonins cause chaperonopathies of great interest within various medical specialties. Although the clinical-genetic aspects of many chaperonopathies are known, the molecular mechanisms causing chaperonin failure and tissue lesions are poorly understood. Progress is necessary to improve treatment, and experimental models that mimic the human situation provide a promising solution. We present two models: one prokaryotic (the archaeon Pyrococcus furiosus) with eukaryotic-like chaperonins and one eukaryotic (Chaetomium thermophilum), both convenient for isolation-study of chaperonins, and report illustrative results pertaining to a pathogenic mutation of CCT5.

Minimal Yet Powerful: The Role of Archaeal Small Heat Shock Proteins in Maintaining Protein Homeostasis

“…In humans, there are 10 different classes of sHsps that are active in different tissues and organs ( Webster et al, 2019 ). Malfunction in these sHsps can lead to several diseases, from cataracts to Alzheimer’s ( Kourtis and Tavernarakis, 2018 ; De Macario et al, 2019 ). Therefore, understanding sHsps role in disease prevention is crucial for therapeutic progress against such diseases.…”

“…Also, a mutation in these sHsps can completely disrupt their structures. The loss of structure can be lethal and leads to no phenotype ( De Macario et al, 2019 ). Therefore, working in a system in which sHsps have a significantly higher tolerance level is preferable.…”

Molecular mechanisms in chaperonopathies: clues to understanding the histopathological abnormalities and developing novel therapies

“…A classification of Hsps/chaperones used in practice and research is based on molecular weight and sorts them into six groups with the following ranges in kDa: 100 or higher, 81-99, 65-80, 55-64, 35-54, and 34 or lower [9], and a standardized nomenclature for Hsps/chaperones has been proposed [10]. Within these groups are families of Hsps/chaperones whose members are evolutionarily related [9,11]; for example, the Hsp90, the Hsp70/DnaK, the chaperonin CCT (chaperonin-containing TCP1), the Hsp40/DnaJ, and the small Hsp families, which belong in the 81-99, 65-80, 55-64, 35-54, and 34-or-lower groups, respectively.…”

“…primary cultures, cell lines, and biopsies as done, for example, for DnaJ/Hsp40 chaperonopathies [96]), or 3D cultures on an artificial matrix as has been done for growth of lung and oral tissues [97,98], and with experimental models, e.g. prokaryotic and eukaryotic models [11].…”