9PNO

Crystal structure of the Streptococcus pneumoniae HtrA protease PDZ domain

9PNO の概要

• エントリーDOI: 10.2210/pdb9pno/pdb
• 分子名称: Trypsin-like serine protease, GLYCEROL (3 entities in total)
• 機能のキーワード: pdz domain, beta sandwich, protein-protease interactions, peptide binding protein
• 由来する生物種: Streptococcus pneumoniae
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 24092.95

構造登録者

Tran, N.,Holyoak, T. (登録日: 2025-07-21, 公開日: 2026-02-11)

主引用文献

Lee, E.,Redzic, J.S.,Gordon, B.,Saviola, A.J.,Tran, N.,Maroney, S.P.,Ashby, N.L.,Shaw, S.,Fulte, S.,McCarty, A.,Holyoak, T.,Meyer, N.,Hansen, K.C.,Clark, S.E.,Eisenmesser, E.
Streptococcus pneumoniae HtrA is a dynamic and monomeric virulence factor capable of forming larger oligomeric complexes.
Protein Sci., 35:e70411-e70411, 2026

PubMed Abstract: High-temperature requirement A (HtrA) proteases are a conserved family of serine proteases central to protein quality control and bacterial virulence. While Gram-negative and human HtrAs are structurally well studied, Gram-positive homologs remain essentially uncharacterized. Here, we present the first integrated structural and mechanistic analysis of a Gram-positive HtrA, from Streptococcus pneumoniae, a virulence factor essential for adhesion and infection in vivo. Proteomic profiling of an htrA knockout and cleavage assays demonstrate that S. pneumoniae HtrA is required for protein quality control, with the PDZ domain mediating substrate recognition. Biochemically, S. pneumoniae HtrA exists exclusively as a monomer in solution, a striking divergence from canonical trimeric HtrAs that we show is shared with other Gram-positive homologs. NMR analyses reveal that the monomer dynamically samples open and closed conformations, while cryo-EM of a catalytic mutant identifies a hexamer stabilized by a unique LoopA-PDZ interaction. Together, these findings define S. pneumoniae HtrA as a dynamic monomer with interdomain coupling between its protease and PDZ domains, establishing Gram-positive HtrAs as a mechanistically divergent subgroup within the HtrA family.

PubMed: 41457497
DOI: 10.1002/pro.70411

実験手法

X-RAY DIFFRACTION (1.85 Å)