title: Structural studies of the N-terminal fragments of the WW domain: Insights into co-translational folding of a beta-sheet protein.
abstract: Nascent proteins fold co-translationally because the folding speed and folding pathways are limited by the rate of ribosome biosynthesis in the living cell. In addition, though full-length proteins can fold all their residues during the folding process, nascent proteins initially fold only with the N-terminal residues. However, the transient structure and the co-translational folding pathway are not well understood. Here we report the atomic structures of a series of N-terminal fragments of the WW domain with increasing amino acid length. Unexpectedly, the structures indicate that the intermediate-length fragments take helical conformations even though the full-length protein has no helical regions. The circular dichroism spectra and theoretical calculations also support the crystallographic results. This suggests that the short-range interactions are more decisive in the structure formation than the long-range interactions for short nascent proteins. In the course of the peptide extension, the helical structure change to the structure mediated by the long-range interactions at a particular polypeptide length. Our results will provide unique information for elucidating the nature of co-translational folding.
authors.affiliation: Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo-ku, Kyoto, 606-8502, Japan.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Hanazono
authors.affiliation: Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo-ku, Kyoto, 606-8502, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Takeda
authors.affiliation: Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo-ku, Kyoto, 606-8502, Japan.
authors.forename: Kunio
authors.initials: K
authors.lastname: Miki
mesh_terms: D000595:Amino Acid Sequence; D003001:Cloning, Molecular; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D005822:Genetic Vectors / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D006860:Hydrogen Bonding; D058619:Maltose-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D000072756:Protein Conformation, alpha-Helical; D000072757:Protein Conformation, beta-Strand; D017510:Protein Folding; D011993:Recombinant Fusion Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D014364:Tryptophan / Q000737:chemistry* / Q000378:metabolism; D000074585:WW Domains
chemical_list: D058619:Maltose-Binding Proteins; D010455:Peptides; D011993:Recombinant Fusion Proteins; D014364:Tryptophan