title: Structure of the N-terminal extension of human aspartyl-tRNA synthetase: implications for its biological function.
abstract: Human aspartyl-tRNA synthetase (hDRS) contains an extension at the N-terminus, which is involved in the transfer of Asp-tRNA to elongation factor alpha1 (EF1alpha). The structure of the N-terminal extension is critical to its function. Conformational studies on the synthetic, 21-residue N-terminal extension peptide (Thr5-Lys25) of human aspartyl-tRNA synthetase using 1H nuclear magnetic resonance (NMR) spectroscopy, showed that the C-terminus adopts a regular alpha-helix with amphiphilicity, while the N-terminus shows a less-ordered structure with a flexible beta-turn. The observed characteristics suggest a structural switch model, such that when the tRNA is in the stretched conformation, the peptide reduces the rate of dissociation of Asp-tRNA from human aspartyl-tRNA synthetase, and provides enough time for elongation factor 1alpha to interact with the Asp-tRNA. Following Asp-tRNA transfer to EF1alpha, the peptide assumes the folded conformation. The structural switch model supports the direct transfer mechanism.
authors.affiliation: Magnetic Resonance Team, Korea Basic Science Institute, Daejeon 305-333, South Korea. cheong@kbsi.re.kr
authors.forename: Hae-Kap
authors.initials: HK
authors.lastname: Cheong
authors.forename: Jin-Young
authors.initials: JY
authors.lastname: Park
authors.forename: Eun-Hee
authors.initials: EH
authors.lastname: Kim
authors.forename: Chulhyun
authors.initials: C
authors.lastname: Lee
authors.forename: Sunghoon
authors.initials: S
authors.lastname: Kim
authors.forename: Youngsoo
authors.initials: Y
authors.lastname: Kim
authors.forename: Byong-Seok
authors.initials: BS
authors.lastname: Choi
authors.forename: Chaejoon
authors.initials: C
authors.lastname: Cheong
mesh_terms: D000595:Amino Acid Sequence; D001226:Aspartate-tRNA Ligase / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D017433:Protein Structure, Secondary; D013329:Structure-Activity Relationship; D020349:Surface Plasmon Resonance
chemical_list: D001226:Aspartate-tRNA Ligase