Visualizing the protein synthesis machinery: New focus on the translational GTPase elongation factor Tu

Rodnina, Marina V.

doi:10.1073/pnas.0812576106

Cited by 7 publications

(8 citation statements)

References 16 publications

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“…Proteins with this type of GTPase can normally be recognized by having a Gln or His following the DxxG/G3 motif. Gln/His (3,49) are believed to stabilize and/or polarize the nucleophilic water relative to the γ-phosphate. Many of the GAPs supply a catalytic residue into the active site and/or stabilize the intrinsic machinery, such as an arginine "finger" (referring to the Arg side chain pointing toward the β-γ-phosphate to stabilize the transition state) or an Gln/Asn "thumb" (the Gln/Asn side chain that replaces the intrinsic GAD: G protein activated by dimerization catalytic Gln of most G domains, called thumb in analogy to the Arg finger) (3,(50)(51)(52)(53).…”

Section: Induction Of the Gtpase Reaction By Gaps Or Homodimerizationmentioning

confidence: 99%

Structure-Function Relationships of the G Domain, a Canonical Switch Motif

Wittinghofer

Vetter

2011

Annu. Rev. Biochem.

411

438

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GTP-binding (G) proteins constitute a class of P-loop (phosphate-binding loop) proteins that work as molecular switches between the GDP-bound OFF and the GTP-bound ON state. The common principle is the 160-180-residue G domain with an α,β topology that is responsible for nucleotide-dependent conformational changes and drives many biological functions. Although the G domain uses a universally conserved switching mechanism, its structure, function, and GTPase reaction are modified for many different pathways and processes.

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Section: Induction Of the Gtpase Reaction By Gaps Or Homodimerizationmentioning

confidence: 99%

Structure-Function Relationships of the G Domain, a Canonical Switch Motif

Wittinghofer

Vetter

2011

Annu. Rev. Biochem.

411

438

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“…Perhaps because the reported structure does not depict the transition state of the GTP hydrolysis reaction, we cannot identify ribosomal components that could directly function in catalysis, despite the proposal that additional catalytic groups may be involved (36). No density was observed for ribosomal protein L7/L12 which is known to be important for stimulating GTP hydrolysis by the ribosome, although perhaps through indirect action (16).…”

Section: Gtpase Activation By the Ribosomementioning

confidence: 99%

The Crystal Structure of the Ribosome Bound to EF-Tu and Aminoacyl-tRNA

Schmeing

Voorhees

Kelley

et al. 2009

Science

486

578

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The ribosome selects a correct tRNA for each amino acid added to the polypeptide chain, as directed by mRNA. Aminoacyl-tRNA is delivered to the ribosome by Elongation Factor-Tu (EFTu), which hydrolyzes GTP and releases tRNA in response to codon recognition. The signaling pathway that leads to GTP hydrolysis upon codon recognition is critical to accurate decoding. Here we present the crystal structure of the ribosome complexed with EF-Tu and aminoacyltRNA, refined to 3.6 Å resolution. The structure reveals details of the tRNA distortion that allows aminoacyl-tRNA to interact simultaneously with the decoding center of the 30S subunit and EFTu at the factor-binding site. A series of conformational changes in EF-Tu and aminoacyl-tRNA suggest a communication pathway between the decoding center and the GTPase center of EF-Tu.

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“…TrGTPase and ribosome are colored in purple and green, respectively; negative charges, the P-loop lysine and the Mg 2+ ion are omitted for clarity. For simplicity, His cat is shown in its neutral form, although it might be double protonated in its activated state (Adamczyk & Warshel, 2011;Liljas et al, 2011;Aleksandrov & Field, 2013;Wallin et al, 2013) (modified from Bos et al, 2007 andRodnina, 2009). C, D The M + ion in eIF5B and aEF1A (purple) is coordinated in a position analogous to the arginine-finger in the complex of Ras (gray) and RasGAP (green) (modified from Bos et al, 2007 andRodnina, 2009 (Warnock et al, 1996;Praefcke & McMahon, 2004;Chappie et al, 2011).…”

Section: The M + Ion As Catalytic Element In the Gtpase Reaction Of Tmentioning

confidence: 99%

“…Analogous catalytic elements provided in cis or in trans have been identified in P-loop GTPases from Ga proteins to MnmE, dynamin and the signal recognition particle (Scrima & Wittinghofer, 2006;Bos et al, 2007;Gasper et al, 2009;Chappie et al, 2010). However, up to now, trGTPases seemed to be an exception among Ras-related G proteins, as the search for an arginine-finger or an analogous catalytic element has been unsuccessful (Wieden et al, 2001;Mohr et al, 2002;Kubarenko et al, 2005;Rodnina, 2009).…”

Section: Introductionmentioning

confidence: 99%

A monovalent cation acts as structural and catalytic cofactor in translational GTP ases

Kuhle

Ficner

2014

The EMBO Journal

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Translational GTPases are universally conserved GTP hydrolyzing enzymes, critical for fidelity and speed of ribosomal protein biosynthesis. Despite their central roles, the mechanisms of GTPdependent 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 GTPcS 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 GTPbound "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 eIF2c, 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.

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Visualizing the protein synthesis machinery: New focus on the translational GTPase elongation factor Tu

Cited by 7 publications

References 16 publications

Structure-Function Relationships of the G Domain, a Canonical Switch Motif

Structure-Function Relationships of the G Domain, a Canonical Switch Motif

The Crystal Structure of the Ribosome Bound to EF-Tu and Aminoacyl-tRNA

A monovalent cation acts as structural and catalytic cofactor in translational GTP ases

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