4RQE

human Seryl-tRNA synthetase dimer complexed with two molecules of tRNAsec

4RQE の概要

• エントリーDOI: 10.2210/pdb4rqe/pdb
• 関連するPDBエントリー: 4rqf
• 分子名称: Serine--tRNA ligase, cytoplasmic, selenocysteine tRNA, SERINE, ... (4 entities in total)
• 機能のキーワード: aminoacyl-trna synthetase, classii aars, aminoacylation, serine, cytosol, ligase-rna complex, ligase/rna
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cytoplasm: P49591
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 178791.30

構造登録者

Xie, W.,Wang, C.,Guo, Y.,Tian, Q.,Jia, Q. (登録日: 2014-11-03, 公開日: 2015-11-04, 最終更新日: 2024-10-30)

主引用文献

Wang, C.,Guo, Y.,Tian, Q.,Jia, Q.,Gao, Y.,Zhang, Q.,Zhou, C.,Xie, W.
SerRS-tRNASec complex structures reveal mechanism of the first step in selenocysteine biosynthesis.
Nucleic Acids Res., 43:10534-10545, 2015

PubMed Abstract: Selenocysteine (Sec) is found in the catalytic centers of many selenoproteins and plays important roles in living organisms. Malfunctions of selenoproteins lead to various human disorders including cancer. Known as the 21st amino acid, the biosynthesis of Sec involves unusual pathways consisting of several stages. While the later stages of the pathways are well elucidated, the molecular basis of the first stage-the serylation of Sec-specific tRNA (tRNA(Sec)) catalyzed by seryl-tRNA synthetase (SerRS)-is unclear. Here we present two cocrystal structures of human SerRS bound with tRNA(Sec) in different stoichiometry and confirm the formation of both complexes in solution by various characterization techniques. We discovered that the enzyme mainly recognizes the backbone of the long variable arm of tRNA(Sec) with few base-specific contacts. The N-terminal coiled-coil region works like a long-range lever to precisely direct tRNA 3' end to the other protein subunit for aminoacylation in a conformation-dependent manner. Restraints of the flexibility of the coiled-coil greatly reduce serylation efficiencies. Lastly, modeling studies suggest that the local differences present in the D- and T-regions as well as the characteristic U20:G19:C56 base triple in tRNA(Sec) may allow SerRS to distinguish tRNA(Sec) from closely related tRNA(Ser) substrate.

PubMed: 26433229
DOI: 10.1093/nar/gkv996

実験手法

X-RAY DIFFRACTION (4 Å)