8DOL

Mechanism of regulation of the Helicobacter pylori Cagbeta ATPase by CagZ

Summary for 8DOL

• Entry DOI: 10.2210/pdb8dol/pdb
• Related: 6JHO
• Descriptor: Cag pathogenicity island protein (Cag5), SULFATE ION, DI(HYDROXYETHYL)ETHER, ... (4 entities in total)
• Functional Keywords: type iv secretion system, cagbeta coupling atpase, cagz, transport protein
• Biological source: Helicobacter pylori 26695
• Total number of polymer chains: 6
• Total formula weight: 404376.07

Authors

Wu, X.,Zhao, Y.,Yang, W.,Sun, L.,Ye, X.,Jiang, M.,Wang, Q.,Wang, Q.,Zhang, X.,Wu, Y. (deposition date: 2022-07-13, release date: 2023-02-15, Last modification date: 2024-04-03)

Primary citation

Wu, X.,Zhao, Y.,Zhang, H.,Yang, W.,Yang, J.,Sun, L.,Jiang, M.,Wang, Q.,Wang, Q.,Ye, X.,Zhang, X.,Wu, Y.
Mechanism of regulation of the Helicobacter pylori Cag beta ATPase by CagZ.
Nat Commun, 14:479-479, 2023

PubMed Abstract: The transport of the CagA effector into gastric epithelial cells by the Cag Type IV secretion system (Cag T4SS) of Helicobacter pylori (H. pylori) is critical for pathogenesis. CagA is recruited to Cag T4SS by the Cagβ ATPase. CagZ, a unique protein in H. pylori, regulates Cagβ-mediated CagA transport, but the underlying mechanisms remain unclear. Here we report the crystal structure of the cytosolic region of Cagβ, showing a typical ring-like hexameric assembly. The central channel of the ring is narrow, suggesting that CagA must unfold for transport through the channel. Our structure of CagZ in complex with the all-alpha domain (AAD) of Cagβ shows that CagZ adopts an overall U-shape and tightly embraces Cagβ. This binding mode of CagZ is incompatible with the formation of the Cagβ hexamer essential for the ATPase activity. CagZ therefore inhibits Cagβ by trapping it in the monomeric state. Based on these findings, we propose a refined model for the transport of CagA by Cagβ.

PubMed: 36717564
DOI: 10.1038/s41467-023-36218-4

Experimental method

X-RAY DIFFRACTION (2.8 Å)