Recent advances in the application of solution NMR spectroscopy to multi-span integral membrane proteins

Abstract

Rougly one-third of all proteins reside in biological membranes. Integral membrane proteins (IMPs), which can only be released from the membrane by disruption of the membrane, perform a host of vital cellular functions as receptors, transporters, channels, electrical and photo-transducers, and so forth. It is therefore not surprising that mutations in membrane proteins are linked to many diseases and that IMPs represent well over 50% of the targets for existing drugs. In spite of the importance of IMPs, the structural biology of this class of proteins remains underdeveloped. As of February 2009 only 1.7% of the structures deposited into the RSB Protein Data Bank were IMPs based on the searches performed by the PDBTM (pdbtm.enzim.hu) and OPM (opm.phar.umich.edu). IMPs can be classified based on the dominant secondary structures of their transmembrane domains, where the number of IMPs of known structure that utilize a-helical spanning elements clearly outnumbers the number of b-barrel proteins by roughly 4:1 (http://pdbtm.enzim.hu and http://opm.phar.umich.edu). Currently deposited structures also show a clear bias regarding the source organism, with 70% from prokaryotic organisms and 30% from eukaryotic organisms (based upon the PDBTM holdings for non-redundant, experimentally determined structures containing at least one transmembrane element). Here we present the recent advances in structural biology of membrane proteins, especailly focusing on solution nmr techniques.