Max Planck Institute of Biophysics, Max-von-Laue-Str. 3, D-60438 Frankfurt am Main, Germany
Compared to the membrane lipids the membrane proteins are the more active players in biological membranes. They catalyze:
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 the membrane.
biological energy transfer and energy conservation in photosynthesis and respiration.
signal reception, signal transduction across the membrane and signal amplification.
reactions by enzymes with preferentially hydrophobic substrates.
Most drugs available to treat diseases act by inhibiting or activating a membrane protein making membrane protein structure determination 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 structures of around 370 membrane proteins are known compared to ten thousands of water soluble proteins. However, the structures of only 20 human membrane proteins (of about 6000 to 8000) could be determined.
The importance of membrane proteins is also evident from the fact that the 2012 Nobel Prize in Chemistry was awarded for functional and structural studies of a membrane protein.
The methods of membrane protein structure determination and several recent successes of the author’s lab with membrane proteins of medical interest will be presented.