9NDJ
Cryo-EM structure of the endogenous ClpP1/ClpP2 heterocomplex from Pseudomonas aeruginosa bound to the AAA+ ClpX unfoldase.
Summary for 9NDJ
| Entry DOI | 10.2210/pdb9ndj/pdb |
| EMDB information | 49274 |
| Descriptor | ATP-dependent Clp protease ATP-binding subunit ClpX, Unknown substrate, ATP-dependent Clp protease proteolytic subunit, ... (7 entities in total) |
| Functional Keywords | clpxp, full-engaged state, aaa protease, chaperone |
| Biological source | Pseudomonas aeruginosa More |
| Total number of polymer chains | 21 |
| Total formula weight | 612644.96 |
| Authors | Ghanbarpour, A.,Zhang, J.J.,Baker, T.A.,Davis, J.H.,Sauer, R.T. (deposition date: 2025-02-18, release date: 2025-10-01, Last modification date: 2026-04-15) |
| Primary citation | Ghanbarpour, A.,Zhang, J.J.,Davis, J.H.,Baker, T.A.,Sauer, R.T. Structural insights into the Pseudomonas aeruginosa ClpP1•ClpP2 heterocomplex and its interactions with the AAA+ ClpX unfoldase. Protein Sci., 34:e70310-e70310, 2025 Cited by PubMed Abstract: ClpXP and other AAA+ proteases play central roles in bacterial proteostasis by degrading misfolded and regulatory proteins. In Pseudomonas aeruginosa, ClpXP consists of the ClpX unfoldase and ClpP peptidase, which influence critical adaptive processes contributing to stress resistance. P. aeruginosa ClpP1 and ClpP2 paralogs assemble into homomeric (ClpP1•ClpP1) and heteromeric (ClpP1•ClpP2) complexes. ClpP2 is only active in the ClpP1•ClpP2 heterocomplex. Here, we present a cryo-EM structure of ClpX•ClpP1•ClpP2, revealing how ClpX binds ClpP1, which in turn interacts with ClpP2. Comparison of the active heterocomplex with an inactive ClpP2 crystal structure shows that ClpP1 binding induces conformational changes in ClpP2, stabilizing an active catalytic triad. Differences in ClpP1 and ClpP2 substrate-binding residues and an unstructured ClpP2 N-terminal segment that protrudes into the peptidase chamber likely contribute to distinct peptide-cleavage specificities of ClpX•ClpP1•ClpP2 and ClpX•ClpP1•ClpP1. Given the role of ClpP1•ClpP2 in biofilm formation and virulence, these structural insights may provide a foundation for developing selective inhibitors to combat P. aeruginosa infections. PubMed: 40980994DOI: 10.1002/pro.70310 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.87 Å) |
Structure validation
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