Sequence similarity as a predictor of the transmembrane topology of membrane-intrinsic subunits of bacterial respiratory chain enzymes.
Integral membrane proteins usually have a predominantly alpha-helical secondary structure in which transmembrane segments are connected by membrane-extrinsic loops. Although a number of membrane protein structures have been reported in recent years, in most cases transmembrane topologies are initially predicted using a variety of theoretical techniques, including hydropathy analyses and the "positive inside" rule. We have explored the use of plots of the distribution of sequence similarity within families of membrane proteins comprising homeomorphic domains as a new method for the prediction/verification of the orientation of transmembrane topology models within certain families of multimeric respiratory chain enzymes. Within such proteins, analyses of sequence similarity can: i) identify heme and/or quinol binding sites; ii) identify potential electron-transfer conduits to/from prosthetic groups; and iii) locate regions defining potential subunit-subunit interactions. We mined emerging bioinformatic data for sequences of 11 families of membrane-intrinsic proteins that are part of multimeric respiratory chain complexes that also have membrane-extrinsic subunits. The sequences of each family were then aligned and the resultant alignments converted into a graphical format recording an empirical measure of the sequence similarity plotted versus residue position. In each case, this plot was compared to the predicted transmembrane topology. With one exception, there is a strong correlation between the existence
Rothery
Richard A
RA
CIHR Group in the Molecular Biology of Membrane Proteins, Department of Biochemistry, University of Alberta, Edmonton, Canada.
Kalra
Navita
N
Turner
Raymond J
RJ
Weiner
Joel H
JH
D000595:Amino Acid Sequence; D001419:Bacteria / Q000201:enzymology*; D002462:Cell Membrane / Q000201:enzymology*; D019295:Computational Biology / Q000379:methods; D004579:Electron Transport; D008565:Membrane Proteins / Q000737:chemistry*; D008954:Models, Biological; D010088:Oxidoreductases / Q000737:chemistry*; D010101:Oxygen Consumption; D011237:Predictive Value of Tests; D011487:Protein Conformation; D016415:Sequence Alignment / Q000379:methods*
D008565:Membrane Proteins; D010088:Oxidoreductases