RT Journal Article
SR Electronic
T1 AAA+ protease-adaptor structures reveal altered conformations and ring specialization
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.02.04.479121
DO 10.1101/2022.02.04.479121
A1 Kim, Sora
A1 Fei, Xue
A1 Sauer, Robert T.
A1 Baker, Tania A.
YR 2022
UL http://biorxiv.org/content/early/2022/02/04/2022.02.04.479121.abstract
AB ClpAP, a two-ring AAA+ protease, degrades N-end-rule proteins bound by the ClpS adaptor. Here, we present high-resolution cryo-EM structures of ClpAPS complexes showing how ClpA pore loops interact with the ClpS N-terminal extension (NTE), which is normally intrinsically disordered. In two structural classes, the NTE is bound by a spiral of pore-1 and pore-2 loops in a manner similar to substrate-polypeptide binding by many AAA+ unfoldases. Kinetic studies reveal that pore-2 loops of the ClpA D1 ring catalyze protein remodeling required for substrate delivery by ClpS. In a third class, D2 pore-1 loops are rotated and tucked away from the channel, and do not bind the NTE, demonstrating asymmetry in engagement by the D1 and D2 rings. These studies demonstrate new structures and functions for key AAA+ elements. In addition to ClpAPS delivery, pore-loop tucking may be used broadly by AAA+ unfoldases, for example during enzyme pausing/unloading.Competing Interest StatementThe authors have declared no competing interest.