PREDICTION OF MEMBRANE-PROTEIN TOPOLOGY UTILIZING MULTIPLE SEQUENCE ALIGNMENTS

A technique for prediction of protein membrane toplogy (intra- and ext raceullular sidedness) has been developed. Membrane-spanning segments are first predicted using an algorithm based upon multiply aligned ami no acid sequences. The compositional differences in the protein segmen ts exposed at each side of the membrane are then investigated. The rat ios are calculated for Asn, Asp, Gly, Phe, Pro, Trp, Tyr, and Val, mos tly found on the extracellular side, and for Ala, Arg, Cys, and Lys, m ostly occurring on the intracellular side. The consensus over these 12 residue distributions is used for sidedness prediction. The method wa s developed with a set of 42 protein families for which all but one we re correctly predicted with the new algorithm. This represents an impr ovement over previous techniques. The new method, applied to a set of 12 membrane protein families different from the test set and with rece ntly determined topologies, performed well, with 11 of 12 sidedness as signments agreeing with experimental results. The method has also been applied to several membrane protein families for which the topology h as yet to be determined. An electronic prediction service is available at the E-mail address tmap@embl-heidelberg.de and on WWW via http://w ww.emblheidelberg.de.