TY - JOUR TI - Head-to-tail interactions of the coiled-coil domains regulate ClpB activity and cooperation with Hsp70 in protein disaggregation AU - Carroni, Marta AU - Kummer, Eva AU - Oguchi, Yuki AU - Wendler, Petra AU - Clare, Daniel K AU - Sinning, Irmgard AU - Kopp, Jürgen AU - Mogk, Axel AU - Bukau, Bernd AU - Saibil, Helen R A2 - Martin, Andreas VL - 3 PY - 2014 DA - 2014/04/30 SP - e02481 C1 - eLife 2014;3:e02481 DO - 10.7554/eLife.02481 UR - https://doi.org/10.7554/eLife.02481 AB - The hexameric AAA+ chaperone ClpB reactivates aggregated proteins in cooperation with the Hsp70 system. Essential for disaggregation, the ClpB middle domain (MD) is a coiled-coil propeller that binds Hsp70. Although the ClpB subunit structure is known, positioning of the MD in the hexamer and its mechanism of action are unclear. We obtained electron microscopy (EM) structures of the BAP variant of ClpB that binds the protease ClpP, clearly revealing MD density on the surface of the ClpB ring. Mutant analysis and asymmetric reconstructions show that MDs adopt diverse positions in a single ClpB hexamer. Adjacent, horizontally oriented MDs form head-to-tail contacts and repress ClpB activity by preventing Hsp70 interaction. Tilting of the MD breaks this contact, allowing Hsp70 binding, and releasing the contact in adjacent subunits. Our data suggest a wavelike activation of ClpB subunits around the ring. KW - single particle EM KW - ClpB/Hsp104 KW - protein unfolding JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -