4DVZ

Crystal structure of the Helicobacter pylori CagA oncoprotein

Summary for 4DVZ

• Entry DOI: 10.2210/pdb4dvz/pdb
• Related: 4DVY
• Descriptor: Cytotoxicity-associated immunodominant antigen (1 entity in total)
• Functional Keywords: oncoprotein
• Biological source: Helicobacter pylori
• Total number of polymer chains: 1
• Total formula weight: 63625.38

Authors

Hayashi, T.,Senda, M.,Morohashi, H.,Higashi, H.,Horio, M.,Kashiba, Y.,Nagase, L.,Sasaya, D.,Shimizu, T.,Venugopalan, N.,Kumeta, H.,Noda, N.,Inagaki, F.,Senda, T.,Hatakeyama, M. (deposition date: 2012-02-23, release date: 2012-07-25, Last modification date: 2024-03-20)

Primary citation

Hayashi, T.,Senda, M.,Morohashi, H.,Higashi, H.,Horio, M.,Kashiba, Y.,Nagase, L.,Sasaya, D.,Shimizu, T.,Venugopalan, N.,Kumeta, H.,Noda, N.N.,Inagaki, F.,Senda, T.,Hatakeyama, M.
Tertiary structure-function analysis reveals the pathogenic signaling potentiation mechanism of Helicobacter pylori oncogenic effector CagA
Cell Host Microbe, 12:20-33, 2012

PubMed Abstract: 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.

PubMed: 22817985
DOI: 10.1016/j.chom.2012.05.010

Experimental method

X-RAY DIFFRACTION (3.19 Å)