PDBsum entry 6oay

Chaperone

PDB id: 6oay

Contents

Protein chains

(+ 0 more) 570 a.a.

26 a.a.

Ligands

AGS ×7

ADP ×4

PDB id:

6oay

Name:

Chaperone

Title:

Structure of the hyperactive clpb mutant k476c, bound to casein, post- state

Structure:

Hyperactive disaggregase clpb. Chain: c, f, e, d, b, a. Engineered: yes. Mutation: yes. Alpha-s1-casein. Chain: p

Source:

Escherichia coli k-12. Organism_taxid: 83333. Expressed in: escherichia coli. Expression_system_taxid: 562. Bos taurus. Bovine. Organism_taxid: 9913

Authors:

A.R.Rizo,J.-B.Lin,S.N.Gates,E.Tse,S.M.Bart,L.M.Castellano,F.Dimaio, J.Shorter,D.R.Southworth

Key ref:

A.N.Rizo et al. (2019). Structural basis for substrate gripping and translocation by the ClpB AAA+ disaggregase. Nat Commun, 10, 2393. PubMed id: 31160557 DOI: 10.1038/s41467-019-10150-y

Date:

18-Mar-19 Release date: 12-Jun-19

Protein chains

P63284  (CLPB_ECOLI) -  Chaperone protein ClpB from Escherichia coli (strain K12)

Seq: 857 a.a.

Struc: 570 a.a.

Protein chain

No UniProt id for this chain

Struc: 26 a.a.

DOI no: 10.1038/s41467-019-10150-y

Nat Commun 10:2393 (2019)

PubMed id: 31160557

Structural basis for substrate gripping and translocation by the ClpB AAA+ disaggregase.

A.N.Rizo, J.Lin, S.N.Gates, E.Tse, S.M.Bart, L.M.Castellano, F.DiMaio, J.Shorter, D.R.Southworth.

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.