Structure of the N-terminal extension of human aspartyl-tRNA synthetase: implications for its biological function.
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.
Cheong
Hae-Kap
HK
Magnetic Resonance Team, Korea Basic Science Institute, Daejeon 305-333, South Korea. cheong@kbsi.re.kr
Park
Jin-Young
JY
Kim
Eun-Hee
EH
Lee
Chulhyun
C
Kim
Sunghoon
S
Kim
Youngsoo
Y
Choi
Byong-Seok
BS
Cheong
Chaejoon
C
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
D001226:Aspartate-tRNA Ligase