A Gradient of ATP Affinities Generates an Asymmetric Power Stroke Driving the Chaperonin TRIC/CCT Folding Cycle

Stefanie Reissmann, Lukasz A. Joachimiak, Bryan Chen, Anne S. Meyer, Anthony Nguyen, Judith Frydman

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

The eukaryotic chaperonin TRiC/CCT uses ATP cycling to fold many essential proteins that other chaperones cannot fold. This 1 MDa hetero-oligomer consists of two identical stacked rings assembled from eight paralogous subunits, each containing a conserved ATP-binding domain. Here, we report a dramatic asymmetry in the ATP utilization cycle of this ring-shaped chaperonin, despite its apparently symmetric architecture. Only four of the eight different subunits bind ATP at physiological concentrations. ATP binding and hydrolysis by the low-affinity subunits is fully dispensable for TRiC function in vivo. The conserved nucleotide-binding hierarchy among TRiC subunits is evolutionarily modulated through differential nucleoside contacts. Strikingly, high- and low-affinity subunits are spatially segregated within two contiguous hemispheres in the ring, generating an asymmetric power stroke that drives the folding cycle. This unusual mode of ATP utilization likely serves to orchestrate a directional mechanism underlying TRiC/CCT@s unique ability to fold complex eukaryotic proteins

Original languageEnglish (US)
Pages (from-to)866-877
Number of pages12
JournalCell Reports
Volume2
Issue number4
DOIs
StatePublished - Oct 25 2012
Externally publishedYes

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Chaperonin Containing TCP-1
Chaperonins
Adenosine Triphosphate
Stroke
Nucleosides
Oligomers
Hydrolysis
Proteins
Nucleotides

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

A Gradient of ATP Affinities Generates an Asymmetric Power Stroke Driving the Chaperonin TRIC/CCT Folding Cycle. / Reissmann, Stefanie; Joachimiak, Lukasz A.; Chen, Bryan; Meyer, Anne S.; Nguyen, Anthony; Frydman, Judith.

In: Cell Reports, Vol. 2, No. 4, 25.10.2012, p. 866-877.

Research output: Contribution to journalArticle

Reissmann, Stefanie ; Joachimiak, Lukasz A. ; Chen, Bryan ; Meyer, Anne S. ; Nguyen, Anthony ; Frydman, Judith. / A Gradient of ATP Affinities Generates an Asymmetric Power Stroke Driving the Chaperonin TRIC/CCT Folding Cycle. In: Cell Reports. 2012 ; Vol. 2, No. 4. pp. 866-877.
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