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

M Michael K. Fenwick (Seattle Structural Genomics Center for Infectious Disease, Seattle Children’s Research Institute) S Stephen J. Mayclin (Seattle Structural Genomics Center for Infectious Disease, Seattle Children’s Research Institute) S Steve Seibold (Seattle Structural Genomics Center for Infectious Disease, Seattle Children’s Research Institute) A Amy E. DeRocher (Seattle Structural Genomics Center for Infectious Disease, Seattle Children’s Research Institute) S Sandhya Subramanian (Seattle Structural Genomics Center for Infectious Disease, Seattle Children’s Research Institute) I Isabelle Q. Phan (Seattle Structural Genomics Center for Infectious Disease, Seattle Children’s Research Institute) D David M. Dranow (Seattle Structural Genomics Center for Infectious Disease, Seattle Children’s Research Institute) D Donald D. Lorimer (Seattle Structural Genomics Center for Infectious Disease, Seattle Children’s Research Institute) A Ariel B. Abramov (Seattle Structural Genomics Center for Infectious Disease, Seattle Children’s Research Institute) R Ryan Choi (Seattle Structural Genomics Center for Infectious Disease, Seattle Children’s Research Institute) S Stephen Nakazawa Hewitt (Seattle Structural Genomics Center for Infectious Disease, Seattle Children’s Research Institute) T Thomas E. Edwards (Seattle Structural Genomics Center for Infectious Disease, Seattle Children’s Research Institute) J James M. Bullard (Chemistry Department, The University of Texas-Pan American) K Kevin P. Battaile (New York Structural Biology Center) I Iwona K. Wower (Department of Animal Sciences, Auburn University) A Aimee C. Soe (Molecular Biophysics and Integrated Bioimaging, Lawrence Berkeley National Laboratory) S Susan E. Tsutakawa S Scott Lovell (Department of Pathology) P Peter J. Myler (Seattle Structural Genomics Center for Infectious Disease, Seattle Children’s Research Institute) J Jacek Wower B Bart L. Staker (Seattle Structural Genomics Center for Infectious Disease, Seattle Children’s Research Institute)

Abstract

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 α-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 Pa GluRS broadens the structural diversity of the GluRS family, and member synthetases of all bacterial AaRS subclasses have now been identified that exhibit oligomerization.

Article Details

Volume / Issue Vol. 122, Issue 19
Published May 13, 2025
ISSN 0027-8424
Publisher National Academy of Sciences

Authors (21)

M

Michael K. Fenwick

Seattle Structural Genomics Center for Infectious Disease, Seattle Children’s Research Institute

S

Stephen J. Mayclin

Seattle Structural Genomics Center for Infectious Disease, Seattle Children’s Research Institute

S

Steve Seibold

Seattle Structural Genomics Center for Infectious Disease, Seattle Children’s Research Institute

A

Amy E. DeRocher

Seattle Structural Genomics Center for Infectious Disease, Seattle Children’s Research Institute

S

Sandhya Subramanian

Seattle Structural Genomics Center for Infectious Disease, Seattle Children’s Research Institute

I

Isabelle Q. Phan

Seattle Structural Genomics Center for Infectious Disease, Seattle Children’s Research Institute

D

David M. Dranow

Seattle Structural Genomics Center for Infectious Disease, Seattle Children’s Research Institute

D

Donald D. Lorimer

Seattle Structural Genomics Center for Infectious Disease, Seattle Children’s Research Institute

A

Ariel B. Abramov

Seattle Structural Genomics Center for Infectious Disease, Seattle Children’s Research Institute

R

Ryan Choi

Seattle Structural Genomics Center for Infectious Disease, Seattle Children’s Research Institute

S

Stephen Nakazawa Hewitt

Seattle Structural Genomics Center for Infectious Disease, Seattle Children’s Research Institute

T

Thomas E. Edwards

Seattle Structural Genomics Center for Infectious Disease, Seattle Children’s Research Institute

J

James M. Bullard

Chemistry Department, The University of Texas-Pan American

K

Kevin P. Battaile

New York Structural Biology Center

I

Iwona K. Wower

Department of Animal Sciences, Auburn University

A

Aimee C. Soe

Molecular Biophysics and Integrated Bioimaging, Lawrence Berkeley National Laboratory

S

Susan E. Tsutakawa

S

Scott Lovell

Department of Pathology

P

Peter J. Myler

Seattle Structural Genomics Center for Infectious Disease, Seattle Children’s Research Institute

J

Jacek Wower

B

Bart L. Staker

Seattle Structural Genomics Center for Infectious Disease, Seattle Children’s Research Institute