Translational GTPases are universally conserved GTP hydrolyzing enzymes, critical for fidelity and speed of ribosomal protein biosynthesis. Despite their central roles, the mechanisms of GTP-dependent conformational switching and GTP hydrolysis that govern the function of trGTPases remain poorly understood. Here, we provide biochemical and high-resolution structural evidence that eIF5B and aEF1A/EF-Tu bound to GTP or GTPgammaS coordinate a monovalent cation (M+) in their active site. Our data reveal that M+ ions form constitutive components of the catalytic machinery in trGTPases acting as structural cofactor to stabilize the GTP-bound "on" state. Additionally, the M+ ion provides a positive charge into the active site analogous to the arginine-finger in the Ras-RasGAP system indicating a similar role as catalytic element that stabilizes the transition state of the hydrolysis reaction. In sequence and structure, the coordination shell for the M+ ion is, with exception of eIF2gamma, highly conserved among trGTPases from bacteria to human. We therefore propose a universal mechanism of M+-dependent conformational switching and GTP hydrolysis among trGTPases with important consequences for the interpretation of available biochemical and structural data.
A monovalent cation acts as structural and catalytic cofactor in translational GTPases.,Kuhle B, Ficner R EMBO J. 2014 Sep 15. pii: e201488517. PMID:25225612[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
↑ Kuhle B, Ficner R. A monovalent cation acts as structural and catalytic cofactor in translational GTPases. EMBO J. 2014 Sep 15. pii: e201488517. PMID:25225612 doi:http://dx.doi.org/10.15252/embj.201488517
