title: Crystal structure of human cytosolic aspartyl-tRNA synthetase, a component of multi-tRNA synthetase complex.
abstract: 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. Here, we report the crystal structure of DRS at a resolution of 2.25 Å. 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. From our analyses of the crystal structure and post-translational modification of DRS, we suggest that the phosphorylation of Ser146 provokes the separation of DRS from the MSC and provides the binding site for an interaction partner with unforeseen functions.
authors.affiliation: Research Institute of Pharmaceutical Sciences, Department of Pharmacy, College of Pharmacy, Seoul National University, Seoul, 151-742, Korea.
authors.forename: Kyung Rok
authors.initials: KR
authors.lastname: Kim
authors.forename: Sang Ho
authors.initials: SH
authors.lastname: Park
authors.forename: Hyoun Sook
authors.initials: HS
authors.lastname: Kim
authors.forename: Kyung Hee
authors.initials: KH
authors.lastname: Rhee
authors.forename: Byung-Gyu
authors.initials: BG
authors.lastname: Kim
authors.forename: Dae Gyu
authors.initials: DG
authors.lastname: Kim
authors.forename: Mi Seul
authors.initials: MS
authors.lastname: Park
authors.forename: Hyun-Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Sunghoon
authors.initials: S
authors.lastname: Kim
authors.forename: Byung Woo
authors.initials: BW
authors.lastname: Han
mesh_terms: D000595:Amino Acid Sequence; D001226:Aspartate-tRNA Ligase / Q000737:chemistry* / Q000378:metabolism; D003460:Crystallization; D004926:Escherichia coli; D057809:HEK293 Cells; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011499:Protein Processing, Post-Translational; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment
chemical_list: D011994:Recombinant Proteins; D001226:Aspartate-tRNA Ligase
keywords: N-helix; aspartyl-tRNA synthetase; crystal structure; multi-tRNA synthetase complex