Research Article

Ratchet-like polypeptide translocation mechanism of the AAA+ disaggregase Hsp104

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Science  21 Jul 2017:
Vol. 357, Issue 6348, pp. 273-279
DOI: 10.1126/science.aan1052

Untangling aggregates one step at a time

Conserved AAA+ protein complexes exploit adenosine triphosphate hydrolysis to unfold and disaggregate their substrates in response to cell stress, but exactly how they do this has been unclear. Gates et al. determined high-resolution cryo-electron microscopy structures of the Hsp104 disaggregase bound to an unfolded polypeptide substrate in its channel. The structures reveal substrate interactions and two different translocation states. Hsp104 undergoes conformational changes that drive movement along the substrate by two-amino-acid steps. These states help explain how this molecular machine can solubilize protein aggregates and amyloids.

Science, this issue p. 273

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