From Protein Structure to Function with Bioinformatics.pdf

94 T. Nugent and D.T. JonesFig. 4.2 A canonical beta-barrel protein, the monomeric porin OmpG from Escherichia coli,viewed from the side. Porins are transmembrane proteins with hollow centres through which smallmolecules can diffuse. PDB code 2f1c4.3 Membrane Proteins Are Difficult to CrystalliseTM proteins, which have both hydrophobic and hydrophilic regions on their surfaces,are much more difficult to isolate than water-soluble proteins, as the nativemembrane surrounding the protein must be disrupted and replaced with detergentmolecules without causing any denaturation. Despite considerable efforts, relativelyfew TM proteins have yielded crystals that diffract to high resolution. Whileit is thought that TM proteins comprise approximately 30% of a proteome, they aresignificantly under-represented in structural databases such as the Protein DataBank (Bernstein et al. 1977) where they comprise only about 1% of total depositedstructures (White 2004). Tables 4.1 and 4.2 summarise the alpha-helical and betabarrelcrystal structures currently available (Lomize et al. 2006b). However, withadvanced technologies such as synchrotron X-ray microscopy becoming available,it is now possible to determine X-ray structures from ever-smaller protein crystals.Combined with novel crystallisation methods such as the use of antibodies to solubiliseproteins, and lipidic phases as crystallisation media, the rate at which TMprotein structures are elucidated should increase over the coming years.4.4 DatabasesA number of databases now exist that serve as repositories for the sequences andstructures of TM proteins. OPM (Lomize et al. 2006b), PDB_TM (Tusnády et al.2005b), CGDB (Sansom et al. 2008), MPDB (Raman et al. 2006) and Stephen White’s