9ARC
Crystal Structure of C0362 (TDE_0362 [TDE0362] resi 205-647)
Summary for 9ARC
| Entry DOI | 10.2210/pdb9arc/pdb |
| Descriptor | Bacterial Ig-like domain protein C0362, POTASSIUM ION (3 entities in total) |
| Functional Keywords | papain-superfamily cysteine protease; virulence factor; tde_0362; alpha/beta hydrolase, hydrolase |
| Biological source | Treponema denticola |
| Total number of polymer chains | 1 |
| Total formula weight | 55638.71 |
| Authors | Clark, N.D.,Malkowski, M.G. (deposition date: 2024-02-23, release date: 2024-11-27, Last modification date: 2025-03-05) |
| Primary citation | 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 Cited by 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: 39753953DOI: 10.1038/s44318-024-00342-8 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.77 Å) |
Structure validation
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