Structural genomics on membrane proteins: the MePNet approach.

Of the 25,000 crystal structure entries deposited in public databases less than 1% are for membrane proteins; this gives a clear indication of the difficulties relating to structural biology and determination of this type of protein. To date, structural genomics networks have mainly focused on soluble proteins, despite the fact that membrane proteins constitute 60 to 70% of current drug targets. Technological improvement on a broad basis is the key to higher success rates, but this is generally not possible unless large functional networks are established. Several structural genomics initiatives, concentrating partly or fully on membrane proteins, have been established during the last few years and the Membrane Protein Network (MePNet; BioXtal, Switzerland) focuses specifically on the pharmaceutically attractive G protein-coupled receptors (GPCRs). Within MePNet, over 100 full-length GPCRs have been subjected to overexpression in bacterial, yeast and mammalian cells, followed by purification and crystallization studies.