PDBsum entry 6oay

Chaperone

PDB id: 6oay

Contents

Protein chains

(+ 0 more) 570 a.a.

26 a.a.

Ligands

AGS ×7

ADP ×4

References listed in PDB file

Key reference

• Title: Structural basis for substrate gripping and translocation by the clpb aaa+ disaggregase.
• Authors: A.N.Rizo, J.Lin, S.N.Gates, E.Tse, S.M.Bart, L.M.Castellano, F.Dimaio, J.Shorter, D.R.Southworth.
• Ref.: Nat Commun, 2019, 10, 2393. [DOI no: 10.1038/s41467-019-10150-y]
• PubMed id: 31160557

Abstract

Bacterial ClpB and yeast Hsp104 are homologous Hsp100 protein disaggregases that serve critical functions in proteostasis by solubilizing protein aggregates. Two AAA+ nucleotide binding domains (NBDs) power polypeptide translocation through a central channel comprised of a hexameric spiral of protomers that contact substrate via conserved pore-loop interactions. Here we report cryo-EM structures of a hyperactive ClpB variant bound to the model substrate, casein in the presence of slowly hydrolysable ATPγS, which reveal the translocation mechanism. Distinct substrate-gripping interactions are identified for NBD1 and NBD2 pore loops. A trimer of N-terminal domains define a channel entrance that binds the polypeptide substrate adjacent to the topmost NBD1 contact. NBD conformations at the seam interface reveal how ATP hydrolysis-driven substrate disengagement and re-binding are precisely tuned to drive a directional, stepwise translocation cycle.