Tunable microsecond dynamics of an allosteric switch regulate the activity of a AAA+ disaggregation machine.
Clicks: 255
ID: 67156
2019
Large protein machines are tightly regulated through allosteric communication channels. Here we demonstrate the involvement of ultrafast conformational dynamics in allosteric regulation of ClpB, a hexameric AAA+ machine that rescues aggregated proteins. Each subunit of ClpB contains a unique coiled-coil structure, the middle domain (M domain), proposed as a control element that binds the co-chaperone DnaK. Using single-molecule FRET spectroscopy, we probe the M domain during the chaperone cycle and find it to jump on the microsecond time scale between two states, whose structures are determined. The M-domain jumps are much faster than the overall activity of ClpB, making it an effectively continuous, tunable switch. Indeed, a series of allosteric interactions are found to modulate the dynamics, including binding of nucleotides, DnaK and protein substrates. This mode of dynamic control enables fast cellular adaptation and may be a general mechanism for the regulation of cellular machineries.
| Reference Key |
mazal2019tunablenature
Use this key to autocite in the manuscript while using
SciMatic Manuscript Manager or Thesis Manager
|
|---|---|
| Authors | Mazal, Hisham;Iljina, Marija;Barak, Yoav;Elad, Nadav;Rosenzweig, Rina;Goloubinoff, Pierre;Riven, Inbal;Haran, Gilad; |
| Journal | Nature communications |
| Year | 2019 |
| DOI | 10.1038/s41467-019-09474-6 |
| URL | |
| Keywords |
Citations
No citations found. To add a citation, contact the admin at info@scimatic.org
Comments
No comments yet. Be the first to comment on this article.