University of Oregon (UO) scientists have discovered how the bacterium Helicobacter pylori navigates through the acidic stomach, opening up new possibilities to inactivate its disease-causing ability without using current strategies that often fail or are discontinued because of side effects. Their report – published online on June 14, 2012 in the journal Structure -- unveils the crystal structure of H. pylori's acid receptor TlpB. The receptor has an external protrusion, identified as a PAS domain, bound by a small molecule called urea and is poised to sense the external environment. TlpB is the first bacterial chemoreceptor of known function shown by crystallography to contain an extracellular PAS domain, the researchers reported. "It is a beautiful structure, and this domain has never been seen before in this class of proteins," said co-author Dr. S. James Remington, professor of physics and member of the UO Institute of Molecular Biology (IMB). Captured at the atomic resolution of 1.38 angstroms, it is the first new, significant structural view in 20 years of the class of receptors used by bacteria to navigate their chemical environment. H. pylori, a Gram-negative bacterium, was first identified in 1982 and shown to be associated with stomach ulcers and stomach cancer. While its mode of transmission is not precisely understood, the bacterium is found in the stomach of half of the people in the world, said co-author Dr. Karen Guillemin, professor of biology and also a member of the IMB. To fight H. pylori infections, patients generally are treated with broad-spectrum antibiotics, but the bacterium is becoming resistant and treatment fails in about 30 percent of cases. As part of the new UO study -- led by postdoctoral researcher Dr. Emily G. Sweeney and doctoral student Dr. J.
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