6OG2

Focus classification structure of the hyperactive ClpB mutant K476C, bound to casein, post-state

Summary for 6OG2

• Entry DOI: 10.2210/pdb6og2/pdb
• Related: 6OAX 6OAY 6OG1 6OG3
• EMDB information: 20004 20005 20049 20050 20051
• Descriptor: Hyperactive disaggregase ClpB, ADENOSINE-5'-DIPHOSPHATE (2 entities in total)
• Functional Keywords: disaggregase, clpb, aaa+, chaperone
• Biological source: Escherichia coli K-12
• Total number of polymer chains: 2
• Total formula weight: 195318.54

Authors

Rizo, A.R.,Lin, J.-B.,Gates, S.N.,Tse, E.,Bart, S.M.,Castellano, L.M.,Dimaio, F.,Shorter, J.,Southworth, D.R. (deposition date: 2019-04-01, release date: 2019-06-12, Last modification date: 2024-03-20)

Primary citation

Rizo, A.N.,Lin, J.,Gates, S.N.,Tse, E.,Bart, S.M.,Castellano, L.M.,DiMaio, F.,Shorter, J.,Southworth, D.R.
Structural basis for substrate gripping and translocation by the ClpB AAA+ disaggregase.
Nat Commun, 10:2393-2393, 2019

PubMed 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.

PubMed: 31160557
DOI: 10.1038/s41467-019-10150-y

Experimental method

ELECTRON MICROSCOPY (4.1 Å)