Role of the individual domains of translation termination factor eRF1 in GTP binding to eRF3

Кононенко, А. Г.; Mitkevich, Vladimir A.; Dubovaya, V. I.; Kolosov, P. M.; Makarov, Alexander А.; Kisselev, Lev L.

doi:10.1002/prot.21544

Cited by 43 publications

(53 citation statements)

References 24 publications

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“…3E) predicted that domain M of eRF1 would contact the GTPase domain of eRF3. Consistent with our modeling result, domain M of eRF1 has been shown to be involved in interaction with eRF3 (Kononenko et al 2008). Interestingly, the predicted interaction between domain M of eRF1 and the switch regions of eRF3 is strikingly similar to the interaction between the regulatory domains of RhoGDI and Cdc42 (Hoffman et al 2000),…”

Section: The Erf1/erf3 Interfacesupporting

confidence: 76%

“…The molecular mechanisms by which eRF1 specifically promotes binding of GTP (but not GDP) to eRF3 and by which it stimulates eRF3's ribosome-dependent GTPase activity are also not understood. Importantly, the C-terminal domain of eRF1, which is mainly responsible for the eRF1/eRF3 interaction, is not sufficient for stimulation of eRF3's GTP-binding and hydrolysis activities, and the M domain of eRF1 is also required for both processes (Kononenko et al 2008).…”

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confidence: 99%

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Structural insights into eRF3 and stop codon recognition by eRF1

Chen¹,

Saito²,

Pisarev³

et al. 2009

Genes Dev.

141

261

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Eukaryotic translation termination is mediated by two interacting release factors, eRF1 and eRF3, which act cooperatively to ensure efficient stop codon recognition and fast polypeptide release. The crystal structures of human and Schizosaccharomyces pombe full-length eRF1 in complex with eRF3 lacking the GTPase domain revealed details of the interaction between these two factors and marked conformational changes in eRF1 that occur upon binding to eRF3, leading eRF1 to resemble a tRNA molecule. Small-angle X-ray scattering analysis of the eRF1/eRF3/GTP complex suggested that eRF1's M domain contacts eRF3's GTPase domain. Consistently, mutation of Arg192, which is predicted to come in close contact with the switch regions of eRF3, revealed its important role for eRF1's stimulatory effect on eRF3's GTPase activity. An ATP molecule used as a crystallization additive was bound in eRF1's putative decoding area. Mutational analysis of the ATP-binding site shed light on the mechanism of stop codon recognition by eRF1.[Keywords: eRF1; eRF3; protein biosynthesis; stop codon recognition; translation termination; translational GTPase] Supplemental material is available at http://www.genesdev.org.

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Section: The Erf1/erf3 Interfacesupporting

confidence: 76%

mentioning

confidence: 99%

Structural insights into eRF3 and stop codon recognition by eRF1

Chen¹,

Saito²,

Pisarev³

et al. 2009

Genes Dev.

141

261

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“…S3). Consistent with biochemical studies (22) and the eRF1-eRF3-GTP model (17), domain M rotates by 37°with respect to eRF1's C-terminal domain, which positions it near eRF3. Domain N is rotated by ∼100°as it reaches into the decoding center.…”

Section: Resultssupporting

confidence: 57%

“…The higher-resolution (∼9.5 Å) cryo-EM structure of the yeast 80S-Dom34-Hbs1-GMPPNP complex revealed a homologous interaction between the middle domain of Dom34 (which is structurally homologous to domain M of eRF1 except that it lacks the GGQ motif) and the G-domain of Hbs1, with the positively charged loop β10-α3 loop of Dom34 directly contacting the switch-1 region of Hbs1 (29). The similarities in overall architecture of the eRF1-eRF3-and Dom34-Hbs1-bound ribosomal complexes in a pre-GTP hydrolysis state suggest a conserved mechanism of ribosome binding and GTP hydrolysis and are consistent with the essential roles of eRF1 and Dom34 in promoting GTP binding and hydrolysis by eRF3 and Hbs1, respectively (5,(18)(19)(20)(21)(22)36).…”

Section: Discussionsupporting

confidence: 48%

“…eRF1 is also strictly required for stimulation of eRF3's ribosomedependent GTPase activity (21). Although the primary determinant of eRF1-eRF3 binding is the interaction between their C-terminal domains, eRF1's domain M contributes additional affinity to the eRF1-eRF3 interaction and is strictly required for stimulation of eRF3's GTP-binding and hydrolysis activities (22). Consistently, the model of eRF1-eRF3-GTP based on the crystal structure of the complex of eRF1 with domains 2 and 3 of eRF3 (eRF3 [2][3] ) and the low-resolution small angle x-ray scattering (SAXS) structure of eRF1-eRF3-GTP (17), predicts that upon binding of eRF1 to eRF3, domain M shifts and rotates, resulting in adoption by eRF1 of a tRNA-like shape.…”

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confidence: 99%

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Cryo-EM structure of the mammalian eukaryotic release factor eRF1–eRF3-associated termination complex

Taylor

Unbehaun

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Eukaryotic translation termination results from the complex functional interplay between two eukaryotic release factors, eRF1 and eRF3, and the ribosome, in which GTP hydrolysis by eRF3 couples codon recognition with peptidyl-tRNA hydrolysis by eRF1. Here, using cryo-electron microscopy (cryo-EM) and flexible fitting, we determined the structure of eRF1-eRF3-guanosine 5′- [β,γ-imido] triphosphate (GMPPNP)-bound ribosomal pretermination complex (pre-TC), which corresponds to the initial, pre-GTP hydrolysis stage of factor attachment. Our results show that eukaryotic translation termination involves a network of interactions between the two release factors and the ribosome. Our structure provides mechanistic insight into the coordination between GTP hydrolysis by eRF3 and subsequent peptide release by eRF1.T ermination of translation occurs when a ribosome reaches the end of the coding region and a stop codon (UAA, UAG, or UGA) enters the aminoacyl tRNA binding site (A site), leaving peptidyl-tRNA in the peptidyl tRNA binding site (P site). It entails stop codon recognition by specialized release factors followed by hydrolysis of peptidyl-tRNA. In eukaryotes, termination is mediated by the concerted action of two directly interacting release factors, eRF1 and eRF3. eRF1 is responsible for stop codon recognition and inducing hydrolysis of peptidyl-tRNA, whereas eRF3, a ribosome-dependent GTPase, strongly stimulates peptide release by eRF1 in a GTP-dependent manner (for review, see ref. 1).eRF1 also participates in ribosome recycling: after peptide release it remains associated with the ribosome and together with ATP-binding cassette sub-family E member 1 (ABCE1) promotes splitting the ribosome into free 60S and tRNA/mRNA-associated 40S subunits (2). eRF1 and eRF3 have paralogs, Dom34 (yeast)/ Pelota (mammals) and Hbs1, respectively, which do not participate in termination but instead play a key role in No-go and nonstop decay surveillance mechanisms (e.g., see refs. 3, 4). Dom34/Pelota and Hbs1 do not induce peptide release in a mechanism similar to eRFs. Instead, they cooperate with ABCE1 to promote dissociation of stalled elongation complexes, which is accompanied by peptidyltRNA drop off (5-7). eRF1 comprises N-terminal (N), middle (M), and C-terminal (C) domains (8). The N domain is responsible for stop codon recognition, which is achieved through a 3D network of conserved residues that include apical TASNIKS (amino acid sequence: threonine-alanine-serine-asparagine-isoleucine-lysine-serine) and YxCxxxF motifs (e.g., refs. 9-12). Domain M contains the universally conserved GGQ motif, which is critical for triggering peptide release: as shown for prokaryotes, its placement into the peptidyl transferase center (PTC) causes rRNA rearrangement, allowing a water molecule to enter (for review, see ref. 13). The rigid core of domain C forms an α-β sandwich (8) that deviates from the standard form by the presence of a small insertion, which forms a minidomain (14). eRF3 consists of an N-terminal sequence (residues 1-...

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Survey of the year 2008: applications of isothermal titration calorimetry

Falconer

Penkova

Jelesarov

et al. 2010

J of Molecular Recognition

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Isothermal titration calorimetry (ITC) is a fast, accurate and label-free method for measuring the thermodynamics and binding affinities of molecular associations in solution. Because the method will measure any reaction that results in a heat change, it is applicable to many different fields of research from biomolecular science, to drug design and materials engineering, and can be used to measure binding events between essentially any type of biological or chemical ligand. ITC is the only method that can directly measure binding energetics including Gibbs free energy, enthalpy, entropy and heat capacity changes. Not only binding thermodynamics but also catalytic reactions, conformational rearrangements, changes in protonation and molecular dissociations can be readily quantified by performing only a small number of ITC experiments. In this review, we highlight some of the particularly interesting reports from 2008 employing ITC, with a particular focus on protein interactions with other proteins, nucleic acids, lipids and drugs. As is tradition in these reviews we have not attempted a comprehensive analysis of all 500 papers using ITC, but emphasize those reports that particularly captured our interest and that included more thorough discussions we consider exemplify the power of the technique and might serve to inspire other users.

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Role of the individual domains of translation termination factor eRF1 in GTP binding to eRF3

Cited by 43 publications

References 24 publications

Structural insights into eRF3 and stop codon recognition by eRF1

Structural insights into eRF3 and stop codon recognition by eRF1

Cryo-EM structure of the mammalian eukaryotic release factor eRF1–eRF3-associated termination complex

Survey of the year 2008: applications of isothermal titration calorimetry

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