An information theoretic framework reveals a tunable allosteric network in group II chaperonins

Lopez, Tom; Dalton, Kevin M.; Tomlinson, A. A. G.; Pande, Vijay S.; Frydman, Judith

doi:10.1038/nsmb.3440

Cited by 13 publications

(11 citation statements)

References 62 publications

(90 reference statements)

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“…5 C. By maintaining next neighbor asymmetry, allosteric communication between alternating subunits with specific behaviors toward ATP allows the nonnative substrate the opportunity to remain in contact with the chaperonin, either by interacting with the apo‐ or ATP‐bound subunits, or by having sufficient time to fold within the chamber. It may be that such asymmetric behavior could provide a way for the Ta thermosome to enhance and modulate its sensitivity to variations in ATP levels under different cellular conditions; this tunable behavior toward ATP might be an intrinsic property of class II chaperonins, as recently proposed by Lopez et al (46). Subunit asymmetry could also reduce the need for full or synchronized lid closure, allowing the accommodation of a greater range of substrate sizes.…”

Section: Discussionmentioning

confidence: 88%

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Intraring allostery controls the function and assembly of a hetero‐oligomeric class II chaperonin

Shoemark¹,

Sessions²,

Brancaccio

et al. 2018

FASEB j.

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Class II chaperonins are essential multisubunit complexes that aid the folding of nonnative proteins in the cytosol of archaea and eukarya. They use energy derived from ATP to drive a series of structural rearrangements that enable polypeptides to fold within their central cavity. These events are regulated by an elaborate allosteric mechanism in need of elucidation. We employed mutagenesis and experimental analysis in concert with in silico molecular dynamics simulations and interface-binding energy calculations to investigate the class II chaperonin from Thermoplasma acidophilum. Here we describe the effects on the asymmetric allosteric mechanism and on hetero-oligomeric complex formation in a panel of mutants in the ATP-binding pocket of the α and β subunits. Our observations reveal a potential model for a nonconcerted folding mechanism optimized for protecting and refolding a range of nonnative substrates under different environmental conditions, starting to unravel the role of subunit heterogeneity in this folding machine and establishing important links with the behavior of the most complex eukaryotic chaperonins.—Shoemark, D. K., Sessions, R. B., Brancaccio, A., Bigotti, M. G. Intraring allostery controls the function and assembly of a hetero-oligomeric class II chaperonin.

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Section: Discussionmentioning

confidence: 88%

“…chaperonins, as recently proposed by Lopez et al (46). Subunit asymmetry could also reduce the need for full or synchronized lid closure, allowing the accommodation of a greater range of substrate sizes.…”

Section: Discussionmentioning

confidence: 89%

Intraring allostery controls the function and assembly of a hetero‐oligomeric class II chaperonin

Shoemark¹,

Sessions²,

Brancaccio

et al. 2018

FASEB j.

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“…6E). These data suggest that for yeast TRiC, only when the diversified subunits assemble together in certain order forming contact TRiC, they can transform into a highly allosterically coordinated machine that can efficiently consume ATP to drive its folding cycle for productive substrate folding (Lopez et al, 2017; Reissmann et al, 2012).…”

Section: Resultsmentioning

confidence: 98%

Cryo-EM study on the homo-oligomeric ring formation of yeast TRiC/CCT subunits reveals TRiC ring assembly mechanism

Wang

Jin

et al. 2021

Preprint

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The complex eukaryotic chaperonin TRiC/CCT helps maintain cellular protein homeostasis, however, its assembly mechanism remains largely unknown. To address the subunit specificity in TRiC assembly, we express each of the individual yeast TRiC subunit in E. coli. Our cryo-EM structural study and biochemical analyses demonstrate that CCT1/2/6 can form TRiC-like homo-oligomeric double ring (HR) complex, however ATP-hydrolysis cannot trigger their ring closure; after deletion of the long N-terminal extension, CCT5 can form the closed double-ring structure; while CCT3/4/7/8 cannot form the HRs. It appears that CCT1 forms a HR in a unique spiral configuration, and ATP-hydrolysis can drive it to re-assemble with an inserted extra subunit-pair. Our data suggest that CCT5 could be the leading subunit in ATP-hydrolysis-driven TRiC ring closure. Moreover, we demonstrate that ADP is sufficient to trigger the assembly of the HRs and TRiC from the assembly intermediate micro-complex form. Our study reveals that through evolution, the more ancestral subunits may have evolved to take more responsibilities in TRiC ring assembly, and we propose a possible assembly mechanism of TRiC involving subunit-pair insertion. Collectively, our study gives hints on the structural basis of subunit specificity in TRiC assembly and cooperativity, beneficial for future TRiC-related therapeutic strategy development.

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“…The evolutionary divergence to eight paralogous subunits further allows TRiC to fine-tune substrate specificity for the various client proteins, through differential recognition modes involving the subunit apical domains 14 and different rates of ATP binding and hydrolysis between subunits 10 , 15 – 18 . The TRiC subunits also contribute to positive cooperativity within each ring and negative cooperativity between rings, resulting in an ATP-dependent allosteric network 19 , 20 that creates asymmetry in conformations 21 , 22 .…”

Section: Mainmentioning

confidence: 99%

Snapshots of actin and tubulin folding inside the TRiC chaperonin

Kelly

Tranter

Pardon

et al. 2022

Nat Struct Mol Biol

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The integrity of a cell’s proteome depends on correct folding of polypeptides by chaperonins. The chaperonin TCP-1 ring complex (TRiC) acts as obligate folder for >10% of cytosolic proteins, including he cytoskeletal proteins actin and tubulin. Although its architecture and how it recognizes folding substrates are emerging from structural studies, the subsequent fate of substrates inside the TRiC chamber is not defined. We trapped endogenous human TRiC with substrates (actin, tubulin) and cochaperone (PhLP2A) at different folding stages, for structure determination by cryo-EM. The already-folded regions of client proteins are anchored at the chamber wall, positioning unstructured regions toward the central space to achieve their native fold. Substrates engage with different sections of the chamber during the folding cycle, coupled to TRiC open-and-close transitions. Further, the cochaperone PhLP2A modulates folding, acting as a molecular strut between substrate and TRiC chamber. Our structural snapshots piece together an emerging model of client protein folding within TRiC.

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An information theoretic framework reveals a tunable allosteric network in group II chaperonins

Cited by 13 publications

References 62 publications

Intraring allostery controls the function and assembly of a hetero‐oligomeric class II chaperonin

Intraring allostery controls the function and assembly of a hetero‐oligomeric class II chaperonin

Cryo-EM study on the homo-oligomeric ring formation of yeast TRiC/CCT subunits reveals TRiC ring assembly mechanism

Snapshots of actin and tubulin folding inside the TRiC chaperonin

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