Tunable microsecond dynamics of an allosteric switch regulate the activity of a AAA+ disaggregation machine.

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ID: 67156
2019
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Abstract
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.
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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
protein translocation hsp110 hsp70 disaggregation j cochaperones brownian ratchet chaperones entropic pulling motor proteins power-stroke

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