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A monovalent cation acts as structural and catalytic cofactor in translational GTP ases
Author(s) -
Kuhle Bernhard,
Ficner Ralf
Publication year - 2014
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201488517
Subject(s) - biology , cofactor , posttranslational modification , gtp' , biochemistry , catalysis , microbiology and biotechnology , biophysics , enzyme
Translational GTP ases 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 tr GTP ases remain poorly understood. Here, we provide biochemical and high‐resolution structural evidence that eIF 5B and aEF 1 A / EF ‐Tu bound to GTP or GTP γS 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‐Ras GAP 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 eIF 2γ, highly conserved among tr GTP ases 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.