Overcoming the challenges of membrane protein crystallography

Abstract

Membrane protein structural biology is still a largely unconquered area, given that approximately 25% of all proteins are membrane proteins and yet less than 150 unique structures are available. Membrane proteins have proven to be difficult to study owing to their partially hydrophobic surfaces, flexibility and lack of stability. The field is now taking advantage of the high-throughput revolution in structural biology and methods are emerging for effective expression, solubilisation, purification and crystallisation of membrane proteins. These technical advances will lead to a rapid increase in the rate at which membrane protein structures are solved in the near future.

Figure 1

Growth of unique membrane protein structures deposited in the PDB. Proteins were found by inspection of the ‘Membrane proteins of known 3D structure’ database [4,5] (http://blanco.biomol.uci.edu/Membrane_Proteins_xtal.html), In blue, the number of structures of prokaryotic membrane proteins, and in yellow, the total number of eukaryotic structures. Both monotopic and multispanning proteins are included. For this study proteins are regarded as unique if they come from the same family but for different species. Structures are not counted in these statistics if they represent mutants, alternative conformations or ligand complexes of a previously counted structure.