Membrane proteins facilitate the transfer of information across lipid bilayers, comprise approximately 25% of a typical proteome, and represent over half of all drug targets. The membrane proteins that mediate interactions between bacterial pathogens and hosts are of particular interest to our laboratory. Invasive bacterial pathogens are responsible for many lethal diseases and epidemics, including plague and meningitis. Although these bacteria have diverse mechanisms of cellular invasion, all of the pathways rely upon interactions between host and bacterial membrane proteins.
Our lab seeks to determine the structure and conformational changes of membrane proteins involved in bacterial infection using a combination of site-directed spin labeling (SDSL), nuclear magnetic resonance (NMR) spectroscopy, and X-ray crystallography, and also to develop tools to accelerate membrane protein structure determination by these methods.
A broad specificity nucleoside kinase from Thermoplasma acidophilum. Elkin SR, Kumar A, Price CW, Columbus L. Proteins. 81, 568-582 (2013).
Endothelial cell expression of haemoglobin α regulates nitric oxide signalling. Straub AC, Lohman AW, Billaud M, Johnstone SR, Dwyer ST, Lee MY, Bortz PS, Best AK, Columbus L, Gaston B, Isakson BE. Nature. 491, 473-7 (2012).
Identification and removal of nitroxide spin label contaminant: impact on PRE studies of α-helical membrane proteins in detergent. Kroncke BM, Columbus L. Protein Science. 21, 589-95 (2012).
Physical Determinants of β-Barrel Membrane Protein Folding in Lipid Vesicles. Dewald AH, Hodges JC, Columbus L. Biophysical Journal. 100, 2131-2140 (2011).
Structural origins of nitroxide side chain dynamics on membrane protein α-helical sites. Kroncke BM, Horanyi PS, Columbus L. Biochemistry. 49, 10045-60 (2010).
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