title: Different protein sequences can give rise to highly similar folds through different stabilizing interactions.
abstract: We report an interesting case of structural similarity between 2 small, nonhomologous proteins, the third domain of ovomucoid (ovomucoid) and the C-terminal fragment of ribosomal L7/L12 protein (CTF). The region of similarity consists of a 3-stranded beta-sheet and an alpha-helix. This region is highly similar; the corresponding elements of secondary structure share a common topology, and the RMS difference for "equivalent" C alpha atoms is 1.6 A. Surprisingly, this common structure arises from completely different sequences. For the common core, the sequence identity is less than 3%, and there is neither significant sequence similarity nor similarity in the position or orientation of conserved hydrophobic residues. This superposition raises the question of how 2 entirely different sequences can produce an identical structure. Analyzing this common region in ovomucoid revealed that it is stabilized by disulfide bonds. In contrast, the corresponding structure in CTF is stabilized in the alpha-helix by a composition of residues with high helix-forming propensities. This result suggests that different sequences and different stabilizing interactions can produce an identical structure.
authors.affiliation: Beckman Laboratories for Structural Biology, Department of Cell Biology, Stanford University School of Medicine, California 94305.
authors.forename: D V
authors.initials: DV
authors.lastname: Laurents
authors.forename: S
authors.initials: S
authors.lastname: Subbiah
authors.forename: M
authors.initials: M
authors.lastname: Levitt
mesh_terms: D000595:Amino Acid Sequence; D004220:Disulfides / Q000737:chemistry; D008969:Molecular Sequence Data; D010059:Ovomucin / Q000737:chemistry*; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012269:Ribosomal Proteins / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid
chemical_list: D004220:Disulfides; D012269:Ribosomal Proteins; D010059:Ovomucin; C016700:ribosomal protein L7-L12