Detecting Protein Function and

ts of the topoisomerase II (1429 residues) might be used to predict that Gyr A and Gyr B interact in E. coli. To find other such putative protein interactions in E. coli, we searched the 4290 protein sequences of the E. coli genome (4) for these patterns of sequence homology (5). We found 6809 pairs of nonhomologous sequences, both members of the pair having significant similarity (6 ) to a single protein in some other genome that we term a Rosetta Stone sequence because it deciphers the interaction between the protein pairs. The 4290 proteins could form at most (4290) 2 /2 # 9 # 10 6 pair interactions, but we would expect many fewer interactions in a functioning cell; roughly 2 to 10 interactions for each protein does not seem unreasonably many. Each of these 6809 pairs is a candidate for a pair of interacting proteins in E. coli. Five such candidates are shown in Fig. 1. The first three pairs of E. coli proteins were among those easily determined from the biochemical literatur