An open axial channel of the AAA ClpXP protease enhances degradation of specific classes of protein substrates.

ABSTRACT: ClpXP and other AAA proteases maintain proteostasis and regulate cellular functions by degrading misfolded, incomplete, or regulatory proteins. ClpX recognizes substrates via unstructured degron sequences, typically located at the N- or C-terminus. Although five classes of degrons are known, only recognition of the ssrA tag, a C-motif-1 degron, is well understood. The ssrA tag initially binds to a conformation of hexameric ClpX in which the axial channel is closed by a pore-2 loop, with subsequent channel opening allowing translocation into and degradation by ClpP. A ClpX variant with a pore-2 loop deletion (ΔNPS) favors the open conformation and exhibits weaker binding to ssrA-tagged substrates. Here, using model substrates representing each of the five known degron classes, we show that

SUBMITTER: Lyu Y 

PROVIDER: S-EPMC12723719 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature