7M1M

Crystal structure of Pseudomonas aeruginosa ClpP1

7M1M の概要

• エントリーDOI: 10.2210/pdb7m1m/pdb
• 分子名称: ATP-dependent Clp protease proteolytic subunit, (4S)-2-METHYL-2,4-PENTANEDIOL (3 entities in total)
• 機能のキーワード: petidase, hydrolase
• 由来する生物種: Pseudomonas aeruginosa
• タンパク質・核酸の鎖数: 14
• 化学式量合計: 325449.75

構造登録者

Mawla, G.D.,Grant, R.A.,Baker, T.A.,Sauer, R.T. (登録日: 2021-03-13, 公開日: 2021-03-24, 最終更新日: 2023-10-18)

主引用文献

Mawla, G.D.,Hall, B.M.,Carcamo-Oyarce, G.,Grant, R.A.,Zhang, J.J.,Kardon, J.R.,Ribbeck, K.,Sauer, R.T.,Baker, T.A.
ClpP1P2 peptidase activity promotes biofilm formation in Pseudomonas aeruginosa.
Mol.Microbiol., 115:1094-1109, 2021

PubMed Abstract: Caseinolytic proteases (Clp) are central to bacterial proteolysis and control cellular physiology and stress responses. They are composed of a double-ring compartmentalized peptidase (ClpP) and a AAA+ unfoldase (ClpX or ClpA/ClpC). Unlike many bacteria, the opportunistic pathogen Pseudomonas aeruginosa contains two ClpP homologs: ClpP1 and ClpP2. The specific functions of these homologs, however, are largely elusive. Here, we report that the active form of PaClpP2 is a part of a heteromeric PaClpP1 P2 tetradecamer that is required for proper biofilm development. PaClpP1 and PaClpP1 P2 complexes exhibit distinct peptide cleavage specificities and interact differentially with P. aeruginosa ClpX and ClpA. Crystal structures reveal that PaClpP2 has non-canonical features in its N- and C-terminal regions that explain its poor interaction with unfoldases. However, experiments in vivo indicate that the PaClpP2 peptidase active site uniquely contributes to biofilm development. These data strongly suggest that the specificity of different classes of ClpP peptidase subunits contributes to the biological outcome of proteolysis. This specialized role of PaClpP2 highlights it as an attractive target for developing antimicrobial agents that interfere specifically with late-stage P. aeruginosa development.

PubMed: 33231899
DOI: 10.1111/mmi.14649

実験手法

X-RAY DIFFRACTION (2.6 Å)