Using X-ray data and advanced computer simulation and visualization software, researchers at the University of Illinois have painstakingly modeled a critical part of a mechanism by which bacteria take up large molecules. Their findings provide a rare window on the complex interplay of proteins involved in the active transport of materials across cell membranes.
Their study, which includes a collaborator from the University of Virginia, appears online in the Biophysical Journal and was described in the May 25 edition of Science.
Transporting large molecules, such as vitamin B12, citric acid or other vital nutrients across the outer membranes of Gram-negative bacteria is not a simple task. The cells must be selective in what substances they take up, and the outer membrane contains no energy-generating machinery to power the job of hauling large molecules inside.
The new study examined an outer membrane transport system that depends on an energy-generating inner membrane protein, TonB. This TonB-dependent transporter (TBDT) contains a beta-barrel domain: a series of parallel sheets that form a tunnel through which large molecules can pass. Another region of the protein, the luminal domain, clogs this barrel until the cell is ready to allow large molecules to pass through.
Crystallographic studies had shown that TonB binds to one end of the luminal domain. Researchers had hypothesized that TonB somehow draws the luminal domain out of the barrel or changes its conformation to make way for the large molecules.
Previous studies had been inconclusive, however. Molecular biologists have difficulty studying systems that involve complex interactions between proteins, particularly when one domain moves into and out of a structure like a beta-barrel, said biochemistry professor Emad Tajkhorshid, principal investigator on the study. Its very difficult to assess this experimentally because they have to look at the accessibility
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Contact: Diana Yates
diya@uiuc.edu
217-333-5802
University of Illinois at Urbana-Champaign
5-Jun-2007