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Conformational dynamics of the Rpt6 ATPase in proteasome assembly and Rpn14 binding.

Juxtaposed to either or both ends of the proteasome core particle (CP) can exist a 19S regulatory particle (RP) that recognizes and prepares ubiquitinated proteins for proteolysis. RP triphosphatase proteins (Rpt1-Rpt6), which are critical for substrate translocation into the CP, bind chaperone-like proteins (Hsm3, Nas2, Nas6, and Rpn14) implicated in RP assembly. We used NMR and other biophysical methods to reveal that S. cerevisiae Rpt6's C-terminal domain undergoes dynamic helix-coil transitions enabled by helix-destabilizing glycines within its two most C-terminal α helices. Rpn14 binds selectively to Rpt6's four-helix bundle, with surprisingly high affinity. Loss of Rpt6's partially unfolded state by glycine substitution (Rpt6 G³⁶⁰,³⁸⁷A) disrupts holoenzyme formation in vitro, an effect enhanced by Rpn14. S. cerevisiae lacking Rpn14 and incorporating Rpt6 G³⁶⁰,³⁸⁷A demonstrate hallmarks of defective proteasome assembly and synthetic growth defects. Rpt4 and Rpt5 exhibit similar exchange, suggesting that conserved structural heterogeneity among Rpt proteins may facilitate RP-CP assembly.

Pubmed ID: 23562395


  • Ehlinger A
  • Park S
  • Fahmy A
  • Lary JW
  • Cole JL
  • Finley D
  • Walters KJ


Structure (London, England : 1993)

Publication Data

May 7, 2013

Associated Grants

  • Agency: NCI NIH HHS, Id: CA097004
  • Agency: NCI NIH HHS, Id: CA136472
  • Agency: NIGMS NIH HHS, Id: GM043601
  • Agency: NCI NIH HHS, Id: R01 CA097004
  • Agency: NCI NIH HHS, Id: R01 CA136472
  • Agency: NIGMS NIH HHS, Id: R01 GM043601

Mesh Terms

  • Adenosine Triphosphatases
  • Binding Sites
  • Carrier Proteins
  • Glycine
  • Models, Molecular
  • Proteasome Endopeptidase Complex
  • Protein Conformation
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins