4TMZ

Translation initiation factor eIF5B (517-858) from C. thermophilum, bound to GTPgammaS and potassium

Summary for 4TMZ

• Entry DOI: 10.2210/pdb4tmz/pdb
• Related: 4TMT 4TMV 4TMW 4TMX 4TN1
• Descriptor: eIF5B, 5'-GUANOSINE-DIPHOSPHATE-MONOTHIOPHOSPHATE, MAGNESIUM ION, ... (7 entities in total)
• Functional Keywords: translation, translation factor, gtpase
• Biological source: Chaetomium thermophilum
• Total number of polymer chains: 2
• Total formula weight: 78108.33

Authors

Kuhle, B.,Ficner, R. (deposition date: 2014-06-02, release date: 2014-09-24, Last modification date: 2024-11-06)

Primary citation

Kuhle, B.,Ficner, R.
A monovalent cation acts as structural and catalytic cofactor in translational GTPases.
Embo J., 33:2547-2563, 2014

PubMed Abstract: 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 GTPγS 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 eIF2γ, 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.

PubMed: 25225612
DOI: 10.15252/embj.201488517

Experimental method

X-RAY DIFFRACTION (2.28 Å)