4DVY: Crystal Structure Of The Helicobacter Pylori Caga Oncoprotein

The Helicobacter pylori type IV secretion effector CagA is a major bacterial virulence determinant and critical for gastric carcinogenesis. Upon delivery into gastric epithelial cells, CagA localizes to the inner face of the plasma membrane, where it acts as a pathogenic scaffold/hub that promiscuously recruits host proteins to potentiate oncogenic signaling. We find that CagA comprises a structured N-terminal region and an intrinsically disordered C-terminal region that directs versatile protein interactions. X-ray crystallographic analysis of the N-terminal CagA fragment (residues 1-876) revealed that the region has a structure comprised of three discrete domains. Domain I constitutes a mobile CagA N terminus, while Domain II tethers CagA to the plasma membrane by interacting with membrane phosphatidylserine. Domain III interacts intramolecularly with the intrinsically disordered C-terminal region, and this interaction potentiates the pathogenic scaffold/hub function of CagA. The present work provides a tertiary-structural basis for the pathophysiological/oncogenic action of H. pylori CagA.
PDB ID: 4DVYDownload
MMDB ID: 102285
PDB Deposition Date: 2012/2/23
Updated in MMDB: 2012/08
Experimental Method:
x-ray diffraction
Resolution: 3.3  Å
Source Organism:
Similar Structures:
Biological Unit for 4DVY: monomeric; determined by author
Molecular Components in 4DVY
Label Count Molecule
Protein (1 molecule)
Cytotoxicity-associated Immunodominant Antigen(Gene symbol: HP0547)
Molecule annotation
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Citing MMDB