5Y2D

Crystal structure of H. pylori HtrA

Summary for 5Y2D

• Entry DOI: 10.2210/pdb5y2d/pdb
• Descriptor: Periplasmic serine endoprotease DegP-like, UNK-UNK-UNK, UNK-UNK-UNK-UNK-UNK, ... (6 entities in total)
• Functional Keywords: serine protease, hydrolase
• Biological source: Helicobacter pylori (Campylobacter pylori); More
• Total number of polymer chains: 6
• Total formula weight: 53148.96

Authors

Zhang, Z.,Huang, Q.,Tao, X. (deposition date: 2017-07-25, release date: 2018-08-15, Last modification date: 2024-03-27)

Primary citation

Zhang, Z.,Huang, Q.,Tao, X.,Song, G.,Zheng, P.,Li, H.,Sun, H.,Xia, W.
The unique trimeric assembly of the virulence factor HtrA fromHelicobacter pylorioccurs via N-terminal domain swapping.
J.Biol.Chem., 294:7990-8000, 2019

PubMed Abstract: Knowledge of the molecular mechanisms of specific bacterial virulence factors can significantly contribute to antibacterial drug discovery. is a Gram-negative microaerophilic bacterium that infects almost half of the world's population, leading to gastric disorders and even gastric cancer. expresses a series of virulence factors in the host, among which high-temperature requirement A (HtrA) is a newly identified serine protease secreted by HtrA cleaves the extracellular domain of the epithelial cell surface adhesion protein E-cadherin and disrupts gastric epithelial cell junctions, allowing to access the intercellular space. Here we report the first crystal structure of HtrA at 3.0 Å resolution. The structure revealed a new type of HtrA protease trimer stabilized by unique N-terminal domain swapping distinct from other known HtrA homologs. We further observed that truncation of the N terminus completely abrogates HtrA trimer formation as well as protease activity. In the presence of unfolded substrate, HtrA assembled into cage-like 12-mers or 24-mers. Combining crystallographic, biochemical, and mutagenic data, we propose a mechanistic model of how HtrA recognizes and cleaves the well-folded E-cadherin substrate. Our study provides a fundamental basis for the development of anti- agents by using a previously uncharacterized HtrA protease as a target.

PubMed: 30936204
DOI: 10.1074/jbc.RA119.007387

Experimental method

X-RAY DIFFRACTION (3.70009854828 Å)