Ĭhaston JJ, Smits C, Aragão D, Wong AS, Ahsan B, Sandin S, Molugu SK, Molugu SK, Bernal RA, Stock D, Stewart AG (2016) Structural and functional insights into the evolution and stress adaptation of Type II chaperonins. Keywordsīouhouche A, Benomar A, Bouslam N, Chkili T, Yahyaoui M (2006) Mutation in the epsilon subunit of the cytosolic chaperonin-containing t-complex peptide-1 (Cct5) gene causes autosomal recessive mutilating sensory neuropathy with spastic paraplegia. We discuss archaeal chaperonins that are similar to those of humans and present an illustrative example of the use of one of these archaeal chaperonins to elucidate the molecular abnormalities generated by a pathogenic mutation in a human chaperonin subunit that causes neuropathy. Here, we report on some archaeal chaperoning systems, focusing on the chaperonins only, which are suitable for standardizing experimental models mimicking the human situations observed in chaperonopathies. Studies are hindered by the extreme complexity of the chaperoning machines and networks in humans and by the scarcity of experimental models. Little is known on the impact of mutations or posttranslational modifications on the properties of the chaperone molecule or on its chaperoning functions. In both instances, the affected chaperones are nonfunctional, or function incorrectly (e.g., gain of function), or their levels/functioning is increased or decreased. The former are caused by mutations of chaperone genes, whereas the acquired chaperonopathies are typically caused by posttranslational modifications of the chaperone proteins. Chaperonopathies are genetic or acquired. Diseases caused by defects in the chaperoning system, named chaperonopathies, are important because many are widespread and frequent and can be life threatening. This range extends from the very simple, consisting of a few genes-proteins in the most primitive archaea to the extremely complex like the one in humans (made of many chaperones, co-chaperones, and chaperone cofactors and close interactors/receptors) and including various degrees of complexity in between. Further refinement of this framework may be necessary because single molecule experiments indicate that there is a great dispersion in the time scales governing the dynamics of the chaperonin cycle.The chaperoning system in organisms across Archaea, Bacteria, and Eukarya encompasses a wide range of complexities. Several scenarios for chaperonin-assisted folding emerge depending on the interplay of the time scales governing the cycle. The model shows, in a natural way, that the time scales in the dynamics of the allosteric transitions are intimately coupled to folding rates of the SP. Force-induced unfolding of the SP puts it on a higher free-energy point in the multidimensional energy landscape from which the SP can either reach the native conformation with some probability or be trapped in one of the competing basins of attraction (i.e., the SP undergoes kinetic partitioning). We conjecture that the unfolding of SP becomes possible because a stretching force is transmitted to the SP when the GroEL particle undergoes allosteric transitions. A key idea in our framework is that, with coordinated ATP hydrolysis and GroES binding, GroEL participates actively by repeatedly unfolding the substrate protein (SP), provided that it is trapped in one of the misfolded states. However, most of the fundamentals of the GroEL action can be described in terms of the single ring. The architecture of GroEL consists of double toroids stacked back-to-back. We describe a conceptual framework for understanding how the GroEL-GroES system assists misfolded proteins to reach their native states. Molecular chaperones are required to assist folding of a subset of proteins in Escherichia coli.

Chaperonin