title: Structural basis of tRNA agmatinylation essential for AUA codon decoding.
abstract: The cytidine at the first position of the anticodon (C34) in the AUA codon-specific archaeal tRNA(Ile2) is modified to 2-agmatinylcytidine (agm(2)C or agmatidine), an agmatine-conjugated cytidine derivative, which is crucial for the precise decoding of the genetic code. Agm(2)C is synthesized by tRNA(Ile)-agm(2)C synthetase (TiaS) in an ATP-dependent manner. Here we present the crystal structures of the Archaeoglobus fulgidus TiaS-tRNA(Ile2) complexed with ATP, or with AMPCPP and agmatine, revealing a previously unknown kinase module required for activating C34 by phosphorylation, and showing the molecular mechanism by which TiaS discriminates between tRNA(Ile2) and tRNA(Met). In the TiaS-tRNA(Ile2)-ATP complex, C34 is trapped within a pocket far away from the ATP-binding site. In the agmatine-containing crystals, C34 is located near the AMPCPP γ-phosphate in the kinase module, demonstrating that agmatine is essential for placing C34 in the active site. These observations also provide the structural dynamics for agm(2)C formation.
authors: Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Ibaraki, Japan.
authors: Takuo
authors: T
authors: Osawa
authors: Satoshi
authors: S
authors: Kimura
authors: Naohiro
authors: N
authors: Terasaka
authors: Hideko
authors: H
authors: Inanaga
authors: Tsutomu
authors: T
authors: Suzuki
authors: Tomoyuki
authors: T
authors: Numata
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D000926:Anticodon / Q000737:chemistry* / Q000378:metabolism; D019843:Archaeal Proteins / Q000737:chemistry / Q000378:metabolism; D019611:Archaeoglobus fulgidus / Q000201:enzymology; D018360:Crystallography, X-Ray; D003562:Cytidine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D007533:Isoleucine-tRNA Ligase / Q000737:chemistry / Q000378:metabolism; D046911:Macromolecular Substances; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D011487:Protein Conformation; D019642:RNA, Archaeal / Q000235:genetics / Q000378:metabolism; D012355:RNA, Transfer, Ile / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D000926:Anticodon; D019843:Archaeal Proteins; D046911:Macromolecular Substances; D019642:RNA, Archaeal; D012355:RNA, Transfer, Ile; C548874:agmatidine; D003562:Cytidine; D000255:Adenosine Triphosphate; D007533:Isoleucine-tRNA Ligase; C002630:alpha,beta-methyleneadenosine 5'-triphosphate