title: NMR structure of a stable "OB-fold" sub-domain isolated from staphylococcal nuclease.
abstract: Similar folds often occur in proteins with dissimilar sequences. The OB-fold forms a part of the structures of at least seven non-homologous proteins that share either oligonucleotide or oligosaccharide binding functions. A 1-103 fragment corresponding to the OB-fold of the 149 amino acid residue staphylococcal nuclease gives NMR spectra characteristic of an unfolded protein, i.e. the wild-type nuclease sequence is insufficient to maintain a stable tertiary structure in the absence of the C-terminal one-third of this single-domain protein. By contrast, the 1-103 fragment of nuclease with the mutations Val66Leu and Gly88Val adopts a stable tertiary structure. The NMR solution structure of this latter fragment is a close variation of the OB-fold found in the X-ray structure of the parent protein. The Val66Leu and Gly88Val mutations appear to stabilize tertiary structure by consolidating the hydrophobic core of the nuclease OB-fold sub-domain. Taken together, these results suggest that recurrent structural motifs such as the OB-fold may in some cases represent vestiges of autonomous folding units that, during evolution, have become integrated into more complex cooperative folding domains.
authors.affiliation: Department of Biological Chemistry, Johns Hopkins Medical Institutions, Baltimore, MD 21205, USA.
authors.forename: A T
authors.initials: AT
authors.lastname: Alexandrescu
authors.forename: A G
authors.initials: AG
authors.lastname: Gittis
authors.forename: C
authors.initials: C
authors.lastname: Abeygunawardana
authors.forename: D
authors.initials: D
authors.lastname: Shortle
mesh_terms: D009682:Magnetic Resonance Spectroscopy; D008836:Micrococcal Nuclease / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D009154:Mutation / Q000502:physiology; D009841:Oligonucleotides / Q000378:metabolism*; D017510:Protein Folding; D017434:Protein Structure, Tertiary
chemical_list: D009841:Oligonucleotides; D008836:Micrococcal Nuclease