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Title | P. aeruginosa CtpA protease adopts a novel activation mechanism to initiate the proteolytic process. |
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Journal, issue, pages | EMBO J, Vol. 43, Issue 8, Page 1634-1652, Year 2024 |
Publish date | Mar 11, 2024 |
Authors | Hao-Chi Hsu / Michelle Wang / Amanda Kovach / Andrew J Darwin / Huilin Li / |
PubMed Abstract | During bacterial cell growth, hydrolases cleave peptide cross-links between strands of the peptidoglycan sacculus to allow new strand insertion. The Pseudomonas aeruginosa carboxyl-terminal ...During bacterial cell growth, hydrolases cleave peptide cross-links between strands of the peptidoglycan sacculus to allow new strand insertion. The Pseudomonas aeruginosa carboxyl-terminal processing protease (CTP) CtpA regulates some of these hydrolases by degrading them. CtpA assembles as an inactive hexamer composed of a trimer-of-dimers, but its lipoprotein binding partner LbcA activates CtpA by an unknown mechanism. Here, we report the cryo-EM structures of the CtpA-LbcA complex. LbcA has an N-terminal adaptor domain that binds to CtpA, and a C-terminal superhelical tetratricopeptide repeat domain. One LbcA molecule attaches to each of the three vertices of a CtpA hexamer. LbcA triggers relocation of the CtpA PDZ domain, remodeling of the substrate binding pocket, and realignment of the catalytic residues. Surprisingly, only one CtpA molecule in a CtpA dimer is activated upon LbcA binding. Also, a long loop from one CtpA dimer inserts into a neighboring dimer to facilitate the proteolytic activity. This work has revealed an activation mechanism for a bacterial CTP that is strikingly different from other CTPs that have been characterized structurally. |
External links | EMBO J / PubMed:38467832 / PubMed Central |
Methods | EM (single particle) |
Resolution | 3.55 - 4.14 Å |
Structure data | EMDB-40846: The C-terminal protease CtpA-LbcA complex of pseudomonas aeruginosa with the TPR at the low position EMDB-40847: The C-terminal protease CtpA-LbcA complex of pseudomonas aeruginosa with the TPR at the high position EMDB-40848: The structure of C-terminal protease CtpA-LbcA complex of Pseudomonas aeruginosa EMDB-40849, PDB-8sxe: EMDB-40850, PDB-8sxf: EMDB-40851, PDB-8sxg: EMDB-40852, PDB-8sxh: |
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Keywords | HYDROLASE / CtpA / LbcA / C-terminal protease / pseudomonas aeruginosa |