Architecture of Pseudomonas aeruginosa glutamyl-tRNA synthetase defines a subfamily of dimeric class Ib aminoacyl-tRNA synthetases

• 成果类型: Article
• 署名作者: Fenwick, Michael K.; Mayclin, Stephen J.; Seibold, Steve; DeRocher, Amy E.; Subramanian, Sandhya; Phan, Isabelle Q.; Dranow, David M.; Lorimer, Donald D.; Abramov, Ariel B.; Choi, Ryan; Hewitt, Stephen Nakazawa; Edwards, Thomas E.; Bullard, James M.; Battaile, Kevin P.; Wower, Iwona K.; Soe, Aimee C.; Tsutakawa, Susan E.; Lovell, Scott; Myler, Peter J.; Wower, Jacek; Staker, Bart L.
• 署名单位: Seattle Children's Hospital; Seattle Children's Hospital; University of Kansas; University of Texas System; University of Texas Rio Grande Valley; Auburn University System; Auburn University; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-13132
• DOI: 10.1073/pnas.2504757122
• 发表日期: 2025-05-13
• 关键词: ribonucleic-acid synthetase; structural genomics center; isoleucyl-transfer-rna; zinc-binding site; escherichia-coli; crystal-structure; editing mechanisms; protein-production; molecular-basis; missing link

摘要

The aminoacyl-tRNA synthetases (AaRSs) are an ancient family of structurally diverse enzymes that are divided into two major classes. The functionalities of most AaRSs are inextricably linked to their oligomeric states. While GluRSs were previously classified as monomers, the current investigation reveals that the form expressed in Pseudomonas aeruginosa is a rotationally pseudosymmetrical homodimer featuring intersubunit tRNA binding sites. Both subunits display a highly bent, pipe strap conformation, with the anticodon binding domain directed toward the active site. The tRNA binding sites are similar in shape to those of the monomeric GluRSs, but are formed through an approximately 180-degree rotation of the anticodon binding domains and dimerization via the anticodon and D-arm binding domains. As a result, each anticodon binding domain is poised to recognize the anticodon loop of a tRNA bound to the adjacent protomer. Additionally, the anticodon binding domain has an alpha- helical C-terminal extension containing a conserved lysine-rich consensus motif positioned near the predicted location of the acceptor arm, suggesting dual functions in tRNA recognition. The unique architecture of PaGluRS broadens the structural diversity of the GluRS family, and member synthetases of all bacterial AaRS subclasses have now been identified that exhibit oligomerization.