7CO2

HtrA-type protease AlgW with tripeptide

7CO2 の概要

• エントリーDOI: 10.2210/pdb7co2/pdb
• 分子名称: TRP-VAL-PHE, AlgW protein, IMIDAZOLE, ... (4 entities in total)
• 機能のキーワード: complex, peptide binding protein
• 由来する生物種: Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 41625.61

構造登録者

Li, T.,Song, Y.J.,Bao, R. (登録日: 2020-08-03, 公開日: 2021-03-10, 最終更新日: 2023-11-29)

主引用文献

Li, T.,Song, Y.,Luo, L.,Zhao, N.,He, L.,Kang, M.,Li, C.,Zhu, Y.,Shen, Y.,Zhao, C.,Yang, J.,Huang, Q.,Mou, X.,Zong, Z.,Yang, J.,Tang, H.,He, Y.,Bao, R.
Molecular Basis of the Versatile Regulatory Mechanism of HtrA-Type Protease AlgW from Pseudomonas aeruginosa.
Mbio, 12:-, 2021

PubMed Abstract: AlgW, a membrane-bound periplasmic serine protease belonging to the HtrA protein family, is a key regulator of the regulated intramembrane proteolysis (RIP) pathway and is responsible for transmitting the envelope stress signals in The AlgW PDZ domain senses and binds the C-terminal of mis-localized outer membrane proteins (OMPs) or periplasmic protein MucE, leading to catalytic activation of the protease domain. While AlgW is functionally well studied, its exact activation mechanism remains to be elucidated. Here, we show that AlgW is a novel HtrA protease that can be biochemically activated by both peptide and lipid signals. Compared with the corresponding homologue DegS in , AlgW exhibits a distinct substrate specificity and regulation mechanism. Structural, biochemical, and mutagenic analyses revealed that, by specifically binding to the C-terminal decapeptide of MucE, AlgW could adopt more relaxed conformation and obtain higher activity than with tripeptide activation. We also investigated the regulatory mechanism of the L loop in AlgW and proved that the unique structural feature of this region was responsible for the distinct enzymatic property of AlgW. These results demonstrate the unique and diverse activation mechanism of AlgW, which may utilize to enhance its adaptability to environmental stress. HtrA-family proteases are commonly employed to sense the protein folding stress and activate the regulated intramembrane proteolysis (RIP) cascade in Gram-negative bacteria. Here, we reveal the unique dual-signal activation and dynamic regulation properties of AlgW, an HtrA-type protease triggering the AlgU stress-response pathway, which controls alginate production and mucoid conversion in The structural and functional data offer insights into the molecular basis underlying the transition of different activation states of AlgW in response to different effectors. Probing these unique features provides an opportunity to correlate the diverse regulation mechanism of AlgW with the high adaptability of to environmental changes during infection.

PubMed: 33622718
DOI: 10.1128/mBio.03299-20

実験手法

X-RAY DIFFRACTION (2.1 Å)