STRUCTURAL-ANALYSIS AND CLASSIFICATION OF LIPOCALINS AND RELATED PROTEINS USING A PROFILE-SEARCH METHOD

A three-dimensional profile method of detecting amino-acid sequences c ompatible with the tertiary structure of any protein has been applied to the lipocalin family of 8-stranded beta-barrels. Profiles derived f rom six well-resolved lipocalin crystal structures were used to search a comprehensive, non-redundant protein sequence database. Each profil e identified a sub-group of lipocalin sequences although no single pro file was sufficient to identify the whole family. The alpha-1-acid gly coprotein sub-family was not identified by any lipocalin profile, indi cating that known sequence differences in otherwise well conserved reg ions of these proteins may be reflected in structural differences. The predicted similarity between the beta-lactoglobulin and alpha-2u-glob ulin structures was much more marked than the similarity between their sequences, and alpha-1-microglobulin sequences were found to be compa tible with the structure of epididymal retinoic acid binding protein w hich has an additional long C-terminal helix. Proteins of unknown stru cture which were predicted to be compatible with the lipocalin fold in clude a human mucin. In cases where a large protein family of low over all sequence similarity contains a small number of known structures, t his technique can be useful in determining or confirming subtle struct ural relationships between family members.