| Autor: |
Rizo, Alexandrea N., Lin, JiaBei, Gates, Stephanie N., Tse, Eric, Bart, Stephen M., Castellano, Laura M., DiMaio, Frank, Shorter, James, Southworth, Daniel R. |
| Zdroj: |
Nature Communications; 6/3/2019, Vol. 10 Issue 1, pN.PAG-N.PAG, 1p |
| Abstrakt: |
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. Bacterial ClpB is a disaggregase that solubilizes protein aggregates. Here the authors present the 2.9 Å cryo-EM structure of a hyperactive variant of ClpB bound to the substrate casein in active translocation states and discuss its polypeptide translocation mechanism. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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