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

摘要

Roughly one-third of all proteins reside in biological membranes [1,2]. 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 [3–5]. 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 [6–9]. 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) [10,11]. IMPs can be classified based on the dominant secondary structures of their transmembrane domains [10,11], 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).