4dvy

Crystal structure of the Helicobacter pylori CagA oncoprotein

spinqualitylabelsall models 4dvy, resolution 3.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4dvy is a 1 chain structure with sequence from Helicobacter pylori 26695. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [CAGA_HELPY] May be necessary for the transcription, folding, export, or function of the cytotoxin. Publication Abstract from PubMed 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. Tertiary Structure-Function Analysis Reveals the Pathogenic Signaling Potentiation Mechanism of Helicobacter pylori Oncogenic Effector CagA.,Hayashi T, Senda M, Morohashi H, Higashi H, Horio M, Kashiba Y, Nagase L, Sasaya D, Shimizu T, Venugopalan N, Kumeta H, Noda NN, Inagaki F, Senda T, Hatakeyama M Cell Host Microbe. 2012 Jul 19;12(1):20-33. PMID:22817985 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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