Crystal structure of human cytosolic aspartyl-tRNA synthetase, a component of multi-tRNA synthetase complex.
Bottom Line: Human cytosolic aspartyl-tRNA synthetase (DRS) catalyzes the attachment of the amino acid aspartic acid to its cognate tRNA and it is a component of the multi-tRNA synthetase complex (MSC) which has been known to be involved in unexpected signaling pathways.DRS is a homodimer with a dimer interface of 3750.5 Å(2) which comprises 16.6% of the monomeric surface area.Our structure reveals the C-terminal end of the N-helix which is considered as a unique addition in DRS, and its conformation further supports the switching model of the N-helix for the transfer of tRNA(Asp) to elongation factor 1α.
Affiliation: Research Institute of Pharmaceutical Sciences, Department of Pharmacy, College of Pharmacy, Seoul National University, Seoul, 151-742, Korea.Show MeSH
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Mentions: In higher eukaryotes, additional domains or motifs in a specific AARS result in new functions. In the case of DRS, KRS, and NRS, they contain the N-helix that is named after the helical conformation in part of their N-terminal extension region.11,23 The previously determined NMR structure of the N-terminal extension of DRS revealed the conformational flexibility caused by the β-turn followed by one α-helix and the N-terminal extension plays a crucial role in the interaction between tRNAAsp and EF-1α.12–14 In our crystal structure, the C-terminal end of the α-helix in the N-terminal extension was observed, comprising Lys26, Glu27, and Arg28 although the N-terminal region was less-ordered. To get a glimpse of the whole N-helix structure, we superposed the structurally well-resolved C-terminal end of the N-terminal extension residue Glu27 and Arg28 with the α-helix of the NMR structure, considering the helical wheel conformation (Supporting Information Fig. S2). The α-helix in the N-terminal extension is amphipathic and the hydrophilic face of the amphipathic helix could interact with positively charged residues Arg8 and Lys9 in the N-terminus by the conformational change on the flexible β-turn.14 Our crystal structure further supports the structural switching model of the N-terminal extension of DRS in the aid of the direct transfer of tRNAAsp to EF-1α [Fig. 2(A)].
Affiliation: Research Institute of Pharmaceutical Sciences, Department of Pharmacy, College of Pharmacy, Seoul National University, Seoul, 151-742, Korea.