Understanding How Microbial Membrane Transporters Work


Membrane transport proteins play a key role in controlling the movement of a wide variety of carbon sources into microbial cells, including complex sugars and plant structural polymers derived from lignin. The transporter profile also influences the composition and structure of microbial communities in soils. However, the functioning of these proteins has not been adequately characterized. Researchers at Argonne National Laboratory have studied a specific type of transporter called the ATP-binding cassette (ABC) proteins. Using a combination of functional characterization (ligand-binding thermal screens), analytical tools for structural analysis (x-ray crystallography), and a computational framework, the functions of ABC transporters have been identified and better defined. The binding strength of various ABC transporters to aromatic products of lignin degradation was determined, and a set of ABC microbial transporters not previously identified with aromatic product transport was found. High-resolution crystal structures were produced for seven of the strongly bound molecular complexes, providing insights into the molecular basis for the observed strong binding. They revealed essential details about the modes of molecular interactions (e.g., hydrogen bonds) and the physical configuration of the active binding site. Knowledge derived from these experiments creates a foundation for developing a sequence-based computational method to predict what molecules will bind similar, but uncharacterized transporters in other microbes.


Michalska, K., C. Chang, J. C. Mack, S. Zerbs, A. Joachimiak, and F. R. Collart. 2012. “Characterization of Transport Proteins for Aromatic Compounds Derived from Lignin: Benzoate Derivative Binding Proteins,” Journal of Molecular Biology 423(4), 555–75. DOI: 10.1016/j.jmb.2012.08.017.