Biological membranes define the cells, and compartmentalize the cells of higher organisms. Consisting of membrane proteins and lipids they are basically impermeable for ions and polar substances, so that electric voltages (“membrane potentials”) and substance gradients across membranes can be generated and maintained. Thus membranes form barriers, and information and substances have to be transferred across these membranes.
Compared to the membrane lipids the membrane proteins are the more active players in biological membranes. They catalyze
(i) transmembrane transport, e.g. the specific uptake of nutrients and substrates, the exchange of ions, and the excretion of waste products and extracellular proteins across biological membranes
(ii) biological electron transfer and energy conservation in photosynthesis and cellular respiration
(iii) signal reception, signal transduction across the membrane and amplification
(iv) enzymatic reactions with preferentially hydrophobic substrates.
It is our aim to understand the function of membrane proteins and their mechanism of action. In addition, most drugs available to treat diseases act by inhibiting or activating a certain membrane protein. Therefore structure determination of membrane proteins is extremely interesting for drug design and virtual screening. However, membrane proteins are difficult to study because of material limitations caused by insufficient availability of membrane proteins and their instability. At present the atomic structures of around 500 membrane proteins are known compared to ten thousands of water soluble proteins. However, only the structures of 50 human membrane proteins (of about 7000) could be determined.
The methods of membrane protein structure determination and several recent successes of the author’s lab with membrane proteins of potential medical interest will be presented.