A monovalent cation acts as structural and catalytic cofactor in translational GTPases

作者：Kuhle Bernhard^*; Ficner Ralf

来源：The EMBO Journal, 2014, 33(21): 2547-2563.

DOI：10.15252/embj.201488517

• catalytic mechanism
• crystal structure
• GTPase
• monovalent cation
• translation

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 GTPS 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 eIF2, 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.

• 出版日期2014-11-3