PREDICTING THE TOPOLOGY OF EUKARYOTIC MEMBRANE-PROTEINS

We show that the so-called 'positive inside' rule, i.e. the observatio n that positively charged amino acids tend to be more prevalent in cyt oplasmic than in extra-cytoplasmic segments in transmembrane proteins [von Heijne, G. (1986) EMBO J. 5, 3021-3027], seems to hold for all po lar segments in multi-spanning eukaryotic membrane proteins irrespecti ve of their position in the sequence and hence can be used in conjunct ion with hydrophobicity analysis to predict their transmembrane topolo gy. Further, as suggested by others, we confirm that the net charge di fference across the first transmembrane segment correlates well with i ts orientation [Hartmann, E., Rapoport, T. A. and Lodish, H. F. (1989) Proc. Natl Acad. Sci. USA 86, 5786-5790], and that the overall amino- acid composition of long polar segments can also be used to predict th eir cytoplasmic or extra-cytoplasmic location [Nakashima, H. and Nishi kawa, K. (1992) FEBS Lett. 303, 141-146]. We present an approach to th e topology prediction problem for eukaryotic membrane proteins based o n a combination of these methods.