TOPOLOGY PREDICTION OF MEMBRANE-PROTEINS

A new method is described for prediction of protein membrane topology (intra- and extracellular sidedness) from multiply aligned amino acid sequences after determination of the membrane-spanning segments. The p rediction technique relies on residue compositional differences in the protein segments exposed at each side of the membrane. Intra/extracel lular ratios are calculated for the residue types Asn, Asp, Gly, Phe, Pro, Trp, Tyr, and Val, preferably found on the extracellular side, an d for Ala, Arg, Cys, and Lys, mostly occurring on the intracellular si de. The consensus over these 12 residue distributions is used for side dness prediction. The method was developed with a test set of 42 prote in families, for which all but one were correctly predicted with the n ew algorithm. This represents an improvement over predictions based on the widely used ''positive-inside rule'' and other techniques, where at least six mispredictions were observed for the same data set. Furth er, application of this and other methods to 12 protein families not i n the test set still showed the better performance of the present tech nique, which was subsequently applied to another set of membrane prote in families where the topology has yet to be determined.