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The sequence determinants of cadherin molecules
Author(s) -
Kister Alexander E.,
Roytberg Michael A,
Chothia Cyrus,
Vasiliev Jurii M.,
Gelfand Israel M.
Publication year - 2001
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1110/ps.37001
Subject(s) - sequence (biology) , cadherin , protein secondary structure , computational biology , structural similarity , sequence analysis , peptide sequence , biology , sequence alignment , domain (mathematical analysis) , sequence logo , conserved sequence , similarity (geometry) , protein family , genetics , computer science , artificial intelligence , mathematics , biochemistry , gene , mathematical analysis , cell , image (mathematics)
Abstract The sequence and structural analysis of cadherins allow us to find sequence determinants—a few positions in sequences whose residues are characteristic and specific for the structures of a given family. Comparison of the five extracellular domains of classic cadherins showed that they share the same sequence determinants despite only a nonsignificant sequence similarity between 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 new method of assigning a sequence to its proper protein family is suggested: analysis of sequence determinants. The main advantage of this method is that 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 family were unequivocally selected from among 80,000 examined proteins. In addition, 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 structure of this domain can serve as the distinguishing characteristics of cadherins.