cell envelope organization / cell envelope / cell wall biogenesis / protein secretion by the type III secretion system / outer membrane-bounded periplasmic space / endopeptidase activity / periplasmic space / serine-type endopeptidase activity / signal transduction / proteolysis / plasma membrane 類似検索 - 分子機能
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
AI136901
米国
引用
ジャーナル: EMBO J / 年: 2024 タイトル: P. aeruginosa CtpA protease adopts a novel activation mechanism to initiate the proteolytic process. 著者: Hao-Chi Hsu / Michelle Wang / Amanda Kovach / Andrew J Darwin / Huilin Li / 要旨: 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.