5Y2D

Crystal structure of H. pylori HtrA


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.70 Å
  • R-Value Free: 0.334 
  • R-Value Work: 0.331 
  • R-Value Observed: 0.332 

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This is version 1.2 of the entry. See complete history


Literature

The unique trimeric assembly of the virulence factor HtrA fromHelicobacter pylorioccurs via N-terminal domain swapping.

Zhang, Z.Huang, Q.Tao, X.Song, G.Zheng, P.Li, H.Sun, H.Xia, W.

(2019) J Biol Chem 294: 7990-8000

  • DOI: https://doi.org/10.1074/jbc.RA119.007387
  • Primary Citation of Related Structures:  
    5Y28, 5Y2D

  • PubMed Abstract: 

    Knowledge of the molecular mechanisms of specific bacterial virulence factors can significantly contribute to antibacterial drug discovery. Helicobacter pylori is a Gram-negative microaerophilic bacterium that infects almost half of the world's population, leading to gastric disorders and even gastric cancer. H. pylori expresses a series of virulence factors in the host, among which high-temperature requirement A ( Hp HtrA) is a newly identified serine protease secreted by H. pylori. Hp HtrA cleaves the extracellular domain of the epithelial cell surface adhesion protein E-cadherin and disrupts gastric epithelial cell junctions, allowing H. pylori to access the intercellular space. Here we report the first crystal structure of Hp 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 Hp HtrA trimer formation as well as protease activity. In the presence of unfolded substrate, Hp HtrA assembled into cage-like 12-mers or 24-mers. Combining crystallographic, biochemical, and mutagenic data, we propose a mechanistic model of how Hp HtrA recognizes and cleaves the well-folded E-cadherin substrate. Our study provides a fundamental basis for the development of anti- H. pylori agents by using a previously uncharacterized HtrA protease as a target.


  • Organizational Affiliation

    MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-sen University, Guangzhou, 510275, China.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Periplasmic serine endoprotease DegP-like465Helicobacter pylori 26695Mutation(s): 0 
Gene Names: hp1018/19
EC: 3.4.21.107
UniProt
Find proteins for G2J5T2 (Helicobacter pylori (strain ATCC 700392 / 26695))
Explore G2J5T2 
Go to UniProtKB:  G2J5T2
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupG2J5T2
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
UNK-UNK-UNK3Helicobacter pylori 26695Mutation(s): 0 
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
UNK-UNK-UNK-UNK-UNK5Helicobacter pylori 26695Mutation(s): 0 
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Entity ID: 4
MoleculeChains Sequence LengthOrganismDetailsImage
UNK-UNK-K-UNK-UNK-UNK-UNK-UNK-UNK-UNK10Helicobacter pylori 26695Mutation(s): 0 
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Entity ID: 5
MoleculeChains Sequence LengthOrganismDetailsImage
UNK-UNK-UNK-UNK-UNK-UNK-UNK-UNK8Helicobacter pylori 26695Mutation(s): 0 
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Entity ID: 6
MoleculeChains Sequence LengthOrganismDetailsImage
UNK-UNK-UNK-UNK-UNK-UNK-UNK-UNK-UNK-UNK-UNK11Helicobacter pylori 26695Mutation(s): 0 
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.70 Å
  • R-Value Free: 0.334 
  • R-Value Work: 0.331 
  • R-Value Observed: 0.332 
  • Space Group: H 3 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 128.88α = 90
b = 128.88β = 90
c = 184.536γ = 120
Software Package:
Software NamePurpose
PHENIXrefinement
HKL-2000data collection
HKL-2000data scaling
PDB_EXTRACTdata extraction
HKL-3000data reduction
PHENIXphasing

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2018-08-15
    Type: Initial release
  • Version 1.1: 2019-08-28
    Changes: Data collection, Database references
  • Version 1.2: 2024-03-27
    Changes: Data collection, Database references