9ARC

Crystal Structure of C0362 (TDE_0362 [TDE0362] resi 205-647)

9ARC の概要

• エントリーDOI: 10.2210/pdb9arc/pdb
• 分子名称: Bacterial Ig-like domain protein C0362, POTASSIUM ION (3 entities in total)
• 機能のキーワード: papain-superfamily cysteine protease; virulence factor; tde_0362; alpha/beta hydrolase, hydrolase
• 由来する生物種: Treponema denticola
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 55638.71

構造登録者

Clark, N.D.,Malkowski, M.G. (登録日: 2024-02-23, 公開日: 2024-11-27, 最終更新日: 2025-03-05)

主引用文献

Kurniyati, K.,Clark, N.D.,Wang, H.,Deng, Y.,Sze, C.W.,Visser, M.B.,Malkowski, M.G.,Li, C.
A bipartite bacterial virulence factor targets the complement system and neutrophil activation.
Embo J., 44:1154-1184, 2025

PubMed Abstract: The complement system and neutrophils constitute the two main pillars of the host innate immune defense against infection by bacterial pathogens. Here, we identify T-Mac, a novel virulence factor of the periodontal pathogen Treponema denticola that allows bacteria to evade both defense systems. We show that T-Mac is expressed as a pre-protein that is cleaved into two functional units. The N-terminal fragment has two immunoglobulin-like domains and binds with high affinity to the major neutrophil chemokine receptors FPR1 and CXCR1, blocking N-formyl-Met-Leu-Phe- and IL-8-induced neutrophil chemotaxis and activation. The C-terminal fragment functions as a cysteine protease with a unique proteolytic activity and structure, which degrades several components of the complement system, such as C3 and C3b. Murine infection studies further reveal a critical T-Mac role in tissue damage and inflammation caused by bacterial infection. Collectively, these results disclose a novel innate immunity-evasion strategy, and open avenues for investigating the role of cysteine proteases and immunoglobulin-like domains of gram-positive and -negative bacterial pathogens.

PubMed: 39753953
DOI: 10.1038/s44318-024-00342-8

実験手法

X-RAY DIFFRACTION (1.77 Å)