Membrane proteins \u2013 receptors, ion channels, transporters, etc. \u2013 constitute about 30% of all proteins in eukaryotic cells. Many of them are targets for current or future drugs. In order to facilitate the basic understanding of the biology of these proteins and in order to aid future rational drug design improved methods are needed to solve the structures of this class of proteins. Since membrane proteins are harder to express and handle than soluble proteins, specialized expression, solubilization, and stabilization techniques are required. Our laboratory is active in all these areas and we are particularly interested in solving structures of membrane proteins by solution NMR spectroscopy. We have determined the very first membrane protein structure that was solved by this technique in 2001, i.e. that of the outer membrane ion channel OmpA.<\/p>\n
We also performed dynamic, thermodynamic, and electrophysiological single channel recording experiments to delineate the gating mechanism of this ion channel.<\/p>\n
In 2007 we determined the structure of the outer membrane porin OmpG by NMR spectroscopy. This is currently one of the largest membrane protein structures ever solved by NMR, (33 kDa, 280 residues).<\/p>\n
More recently, we solved the structures of OprH and OprG from Pseudomonas aeruginosa. We found that OprG is a facilitator for small amino acid transport in the outer membrane of this clinically important pathogen. We also\u00a0 determined the interaction of OprH with lipopolysaccharide (LPS) by NMR. The tight OprH-LPS interaction has been implicated in forming an unusually tough outer membrane and thereby conferring antibiotic resistance. These studies will help us to understand and improve antibiotic treatment of Pseudomonas infections.<\/p>\n
The methods that we are developing with these proteins should also be helpful to tackle more difficult projects in the future like helical membrane receptors and ion channels that have been identified as potential drug targets.<\/p>\n\n\t\t