The sequence determinants of cadherin molecules

The sequence and structural analysis of cadherins. allow us to find sequenc e determinants-a few positions in sequences whose residues are characterist ic and specific for the structures of a given family. Comparison of the fiv e extracellular domains of classic cadherins showed that they share the sam e sequence determinants despite only a nonsignificant sequence similarity b etween the N-terminal domain and other extracellular domains. This allowed us to predict secondary structures and propose three-dimensional structures for these domains that have not been structurally analyzed previously. A n ew method of assigning a sequence to its proper protein family is suggested : analysis of sequence determinants. The main advantage of this method is t hat it is not necessary to know all or almost all residues in a sequence as required for other traditional classification tools such as BLAST, FASTA, and Hmm. Using the key positions only, that is, residues that serve as the sequence determinants, we found that all members of the classic cadherin fa mily were unequivocally selected from among 80,000 examined proteins. In ad dition, we proposed a model for the secondary structure of the cytoplasmic domain of cadherins based on the principal relations between sequences and secondary structure multialignments. The patterns of the secondary structur e of this domain can serve as the distinguishing characteristics of cadheri ns.