Structure and Function of the Cytosolic Chaperonin CCT

Valpuesta, José; Carrascosa, José L.; Willison, Keith R.

doi:10.1002/9783527619498.ch54

Cited by 27 publications

(36 citation statements)

References 145 publications

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“…The archaebacterial thermosome and CCT chaperonins were characterized later than GroEL and clearly they constitute a separate group that shows strong sequence and structural homology (Valpuesta et al 2005). The chaperonin family is now broadly separated into two types, I and II, mainly based on evolutionary Figure 1.…”

Section: Chaperoninsmentioning

confidence: 99%

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Development of free-energy-based models for chaperonin containing TCP-1 mediated folding of actin

Altschuler

Willison

2008

J. R. Soc. Interface.

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A free-energy-based approach is used to describe the mechanism through which chaperonincontaining TCP-1 (CCT) folds the filament-forming cytoskeletal protein actin, which is one of its primary substrates. The experimental observations on the actin folding and unfolding pathways are collated and then re-examined from this perspective, allowing us to determine the position of the CCT intervention on the actin free-energy folding landscape. The essential role for CCT in actin folding is to provide a free-energy contribution from its ATP cycle, which drives actin to fold from a stable, trapped intermediate I 3 , to a less stable but now productive folding intermediate I 2 . We develop two hypothetical mechanisms for actin folding founded upon concepts established for the bacterial type I chaperonin GroEL and extend them to the much more complex CCT system of eukaryotes. A new model is presented in which CCT facilitates free-energy transfer through direct coupling of the nucleotide hydrolysis cycle to the phases of actin substrate maturation.

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Section: Chaperoninsmentioning

confidence: 99%

“…The subject of this article is the chaperonin found in eukaryotic cytosol, the chaperonin-containing TCP-1 (CCT). CCT is a uniquely complex chaperonin intimately involved in actin and tubulin cytoskeletal protein folding (Valpuesta et al 2005;Horwich et al 2007).…”

Section: Introductionmentioning

confidence: 99%

Development of free-energy-based models for chaperonin containing TCP-1 mediated folding of actin

Altschuler

Willison

2008

J. R. Soc. Interface.

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“…Although a KNF model has been described for inter-ring signaling in the two chaperonin groups [83], there are differences between them, probably linked to the variations in inter-ring structure described above. ATP saturation of the two rings in Group I results in decreased ATP hydrolysis [26], probably due to steric clash caused by simultaneous ATP hydrolysis in both.…”

Section: Allosterymentioning

confidence: 99%

“…First, unlike the rest of the chaperonins, CCT is not promiscuous, but seems to act on a limited, albeit large group of client proteins, in particular actin and tubulin [4,83,90]. Many other client proteins with very different native structures interact with CCT, so a common pattern of CCT-substrate interaction cannot be deduced.…”

Section: Conformational Changes and Reaction Cyclementioning

confidence: 99%

“…The second important difference from the rest of the chaperonins is that, to achieve its functions, CCT is assisted by a large number of co-chaperones [4,83]. Prefoldin (PFD) is common to all Group II chaperonins (although the CCT-assisting PFD is also more complex than its archaeal counterpart; [93]); in addition, CCT interacts with the major chaperone Hsp70, which delivers substrates such as the Von Hippel-Lindau tumor suppressor protein (VHL) [94,95].…”

Section: Conformational Changes and Reaction Cyclementioning

confidence: 99%

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Dynamics, flexibility, and allostery in molecular chaperonins

et al. 2015

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a b s t r a c tThe chaperonins are a family of molecular chaperones present in all three kingdoms of life. They are classified into Group I and Group II. Group I consists of the bacterial variants (GroEL) and the eukaryotic ones from mitochondria and chloroplasts (Hsp60), while Group II consists of the archaeal (thermosomes) and eukaryotic cytosolic variants (CCT or TRiC). Both groups assemble into a dual ring structure, with each ring providing a protective folding chamber for nascent and denatured proteins. Their functional cycle is powered by ATP binding and hydrolysis, which drives a series of structural rearrangements that enable encapsulation and subsequent release of the substrate protein.Chaperonins have elaborate allosteric mechanisms to regulate their functional cycle. Long-range negative cooperativity between the two rings ensures alternation of the folding chambers. Positive intra-ring cooperativity, which facilitates concerted conformational transitions within the protein subunits of one ring, has only been demonstrated for Group I chaperonins. In this review, we describe our present understanding of the underlying mechanisms and the structurefunction relationships in these complex protein systems with a particular focus on the structural dynamics, allostery, and associated conformational rearrangements.

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Molecular determinants of the ATP hydrolysis asymmetry of the CCT chaperonin complex

et al. 2014

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The eukaryotic cytosolic chaperonin CCT is a molecular machine involved in assisting the folding of proteins involved in important cellular processes. Like other chaperonins, CCT is formed by a double-ring structure but, unlike all of them, each ring is composed of eight different, albeit homologous subunits. This complexity has probably to do with the specificity in substrate interaction and with the mechanism of protein folding that takes place during the chaperonin functional cycle, but its detailed molecular basis remains unknown. We have analyzed the known proteomes in search of residues that are differentially conserved in the eight subunits, as predictors of functional specificity (specificity-determining positions; SDPs). We have found that most of these SDPs are located near the ATP binding site, and that they define four CCT clusters, corresponding to subunits CCT3, CCT6, CCT8 and CCT1/2/4/5/7. Our results point to a spatial organisation of the CCT subunits in two opposite areas of the ring and provide a molecular explanation for the previously described asymmetry in the hydrolysis of ATP.

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Structure and Function of the Cytosolic Chaperonin CCT

Cited by 27 publications

References 145 publications

Development of free-energy-based models for chaperonin containing TCP-1 mediated folding of actin

Development of free-energy-based models for chaperonin containing TCP-1 mediated folding of actin

Dynamics, flexibility, and allostery in molecular chaperonins

Molecular determinants of the ATP hydrolysis asymmetry of the CCT chaperonin complex

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