title: Crystal structure of human mitochondrial tyrosyl-tRNA synthetase reveals common and idiosyncratic features.
abstract: We report the structure of a strictly mitochondrial human synthetase, namely tyrosyl-tRNA synthetase (mt-TyrRS), in complex with an adenylate analog at 2.2 A resolution. The structure is that of an active enzyme deprived of the C-terminal S4-like domain and resembles eubacterial TyrRSs with a canonical tyrosine-binding pocket and adenylate-binding residues typical of class I synthetases. Two bulges at the enzyme surface, not seen in eubacterial TyrRSs, correspond to conserved sequences in mt-TyrRSs. The synthetase electrostatic surface potential differs from that of other TyrRSs, including the human cytoplasmic homolog and the mitochondrial one from Neurospora crassa. The homodimeric human mt-TyrRS shows an asymmetry propagating from the dimer interface toward the two catalytic sites and extremities of each subunit. Mutagenesis of the catalytic domain reveals functional importance of Ser200 in line with an involvement of A73 rather than N1-N72 in tyrosine identity.
authors.affiliation: Département Machineries Traductionnelles, Architecture et Réactivité de l'ARN, Université Louis Pasteur de Strasbourg, CNRS, IBMC, 15 rue René Descartes, 67084 Strasbourg, France.
authors.forename: Luc
authors.initials: L
authors.lastname: Bonnefond
authors.forename: Magali
authors.initials: M
authors.lastname: Frugier
authors.forename: Elodie
authors.initials: E
authors.lastname: Touzé
authors.forename: Bernard
authors.initials: B
authors.lastname: Lorber
authors.forename: Catherine
authors.initials: C
authors.lastname: Florentz
authors.forename: Richard
authors.initials: R
authors.lastname: Giegé
authors.forename: Claude
authors.initials: C
authors.lastname: Sauter
authors.forename: Joëlle
authors.initials: J
authors.lastname: Rudinger-Thirion
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D018360:Crystallography, X-Ray; D006801:Humans; D008928:Mitochondria / Q000201:enzymology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D012343:RNA, Transfer / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D014448:Tyrosine-tRNA Ligase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D012343:RNA, Transfer; D014448:Tyrosine-tRNA Ligase