Membrane proteins: Structure and mechanisms

Prof. Dr. Werner Kühlbrandt, Director

Membrane proteins are fascinating.  Embedded in the membrane that surrounds every living cell and the compartments within it, they perform a vast range of different functions, which are central to life.  None of these vital processes can be fully understood without knowing, ideally in atomic detail, what the proteins look like.  Often, the structures of at least two different states need to be known, especially of membrane proteins that undergo conformational changes in performing their function, for example proteins active in membrane transport.

Due to their special position in the lipid bilayer, the exterior surface of membrane proteins is partly hydrophobic – the part that is embedded in the lipid bilayer – while the parts exposed to the aqueous cytoplasm or the surrounding medium are hydrophilic, like normal soluble proteins. This means that membrane proteins are a particular challenge for structural biology, which adds to their attraction.

Currently, membrane proteins account for less than 0.5% of all entries in the protein data bank, whereas 20-30% of all genes in all organisms are thought to encode membrane proteins. Therefore a great deal remains to be done. Although the situation has improved over the past few years, there is still an immense need for more, and more detailed structural studies.

The Max Planck Institute of Biophysics is a well-known centre for studying all aspects of membrane proteins, and researchers at this institute have made ground-breaking contributions to this field. Our Department of Structural Biology is especially interested in proteins and large complexes involved in membrane transport, biological energy conversion, and membrane biogenesis. We investigate the structure of these proteins by electron and X-ray crystallography as well as by single-particle cryo-EM. Increasingly, we are also studying the structure, interactions and distribution of the large membrane proteins complexes in situ by electron cryo-tomography, and of large soluble complexes by high-resolution single-particle cryo-EM.

We produce most of the membranes, membrane proteins and complexes for structural studies ourselves, but some are made by outside collaborators. Expression, purification and crystallization of membrane proteins are demanding tasks that have to be re-optimized for each new protein. This accounts for a considerable part of our research effort. We grow both two-dimensional (2D) crystals for electron crystallography, as well as 3D crystals for X-ray crystallography, and then take the course that looks most promising for structure determination. Often 2D crystals form first, but they are usually not well enough ordered for high-resolution work. 3D crystallization of membrane proteins has become more tractable in recent years, due to the widespread use of special sparse matrix screens and crystallization robots that can handle small volumes. However, each protein presents a new challenge, and improving crystals from the first exciting hits to specimens suitable for high-resolution data collection can still take years of dedicated, painstaking work.

Contact:

Max Planck Institute of Biophysics

Prof. Dr. Werner Kühlbrandt, Director
Department of Structural Biology
Secretary: Monika Hobrack

Phone: +49 (0) 69 6303-3001
Fax: +49 (0) 69 6303-3002
E-mail: monika.hobrack(at)biophys.mpg.de