6og2

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

6og2, resolution 4.10Å Show:Asymmetric Unit Biological Assembly Structural highlights 6og2 is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: Related: 6og1, 6og3, 6oax, 6oay Experimental data: Check Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed 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 ATPgammaS, 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. Structural basis for substrate gripping and translocation by the ClpB AAA+ disaggregase.,Rizo AN, Lin J, Gates SN, Tse E, Bart SM, Castellano LM, DiMaio F, Shorter J, Southworth DR Nat Commun. 2019 Jun 3;10(1):2393. doi: 10.1038/s41467-019-10150-y. PMID:31160557 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.