Crystal Structures of the Ribosome in Complex with Release Factors RF1 and RF2 Bound to a Cognate Stop Codon

Petry, Sabine; Brodersen, D.E.; Murphy, F.V.; Dunham, C.M.; Selmer, M.; Tarry, M.J.; Kelley, A.C.; Ramakrishnan, V.

doi:10.1016/j.cell.2005.09.039

Cited by 237 publications

(260 citation statements)

References 58 publications

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“…As an example, as shown in Figure 5B (previously unpublished), a change from +4 G to U following the UAA stop codon enhances the strength of the crosslink between the first base of the stop codon and RF1, which preferentially recognizes these stop codons. Petry et al [32] observed that electron density attributable to the decoding RF extends to the fourth base of the termination signal, as we predicted from our biochemical studies. X-ray studies with mRNA complexed with cognate and non-cognate tRNA on the ribosome gave great insight into how structural changes in nucleotides of the rRNA in particular were important for decoding fidelity, with the rRNA acting as a sensor for correct codon/anticodon pairing that was particularly stringent at the first and second base positions.…”

Section: Is the Decoding Rf More Promiscuous Than A Trna In Its Contasupporting

confidence: 71%

“…The RF2 structure presented a puzzling paradox as to how the RF functioned on the ribosome. Further experiments have resolved this paradox by revealing that the molecule undergoes a highly significant conformational change [19,[30][31][32][33].…”

Section: Is the Decoding Rf A Trna Mimic?mentioning

confidence: 99%

“…Nevertheless, we did not publish details of the crosslink site on the RF since there was no supporting biochemical evidence or a contextual biological explanation. Recently, however, with the publication of the compelling X-ray structure of the bacterial termination complex by Petry et al [32], this has been provided. While it was not possible to resolve the electron density of the anticodon loop from that of the stop codon due to the medium resolution of the crystal structures, in this depiction there was an unexpected feature, the a5 helix/loop on the factor containing the DIQ sequence was oriented towards the first base in a manner that could explain why a crosslink directed away from a moiety within this base of the stop codon might have occurred with this sequence on the protein.…”

Section: How Do the Bacterial Rfs Function At The Decoding Site?mentioning

confidence: 99%

“…Petry et al [32] were able to obtain stable ribosomal complexes with RF only when a tRNA occupied the P site and mRNA was present in the complex. This implies that the tRNA is contributing to the stability of the RF binding either indirectly by stabilising the conformation of the ribosome or directly by providing a binding face for the RF.…”

Section: Is the Decoding Rf More Promiscuous Than A Trna In Its Contamentioning

confidence: 99%

“…The X-ray structure of the termination complex [32] modelled the loop containing the SPF motif of RF2 (PXT of RF1) into the decoding site. In the modelled structure, the discriminatory motif was in the near vicinity but not in close contact with the second and third bases of the stop codon as predicted although it is likely the region is restructured when the termination complex forms (see Figure 2B).…”

Section: Is the Decoding Rf More Promiscuous Than A Trna In Its Contamentioning

confidence: 99%

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Accommodating the bacterial decoding release factor as an alien protein among the RNAs at the active site of the ribosome

et al. 2007

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The decoding release factor (RF) triggers termination of protein synthesis by functionally mimicking a tRNA to span the decoding centre and the peptidyl transferase centre (PTC) of the ribosome. Structurally, it must fit into a site crafted for a tRNA and surrounded by five other RNAs, namely the adjacent peptidyl tRNA carrying the completed polypeptide, the mRNA and the three rRNAs. This is achieved by extending a structural domain from the body of the protein that results in a critical conformational change allowing it to contact the PTC. A structural model of the bacterial termination complex with the accommodated RF shows that it makes close contact with the first, second and third bases of the stop codon in the mRNA with two separate loops of structure: the anticodon loop and the loop at the tip of helix a5. The anticodon loop also makes contact with the base following the stop codon that is known to strongly influence termination efficiency. It confirms the close contact of domain 3 of the protein with the key RNA structures of the PTC. The mRNA signal for termination includes sequences upstream as well as downstream of the stop codon, and this may reflect structural restrictions for specific combinations of tRNA and RF to be bound onto the ribosome together. An unbiased SELEX approach has been investigated as a tool to identify potential rRNA-binding contacts of the bacterial RF in its different binding conformations within the active centre of the ribosome.

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Section: Is the Decoding Rf More Promiscuous Than A Trna In Its Contasupporting

confidence: 71%

Section: Is the Decoding Rf A Trna Mimic?mentioning

confidence: 99%

Section: How Do the Bacterial Rfs Function At The Decoding Site?mentioning

confidence: 99%

Section: Is the Decoding Rf More Promiscuous Than A Trna In Its Contamentioning

confidence: 99%

Section: Is the Decoding Rf More Promiscuous Than A Trna In Its Contamentioning

confidence: 99%

See 3 more Smart Citations

Accommodating the bacterial decoding release factor as an alien protein among the RNAs at the active site of the ribosome

et al. 2007

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Ribosomal Proteins: Role in Ribosomal Functions

Nikolay

Bruck

Achenbach

et al. 2015

Encyclopedia of Life Sciences

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The assignment of specific ribosomal functions to individual ribosomal proteins is difficult due to the enormous cooperativity of the ribosome; however, important roles for distinct ribosomal proteins are becoming evident. Although ribosomal ribonucleic acid (rRNA) has the major claim to certain aspects of ribosome function, such as decoding and peptidyltransferase activity, there are also protein‐dominated functional hot‐spots on the ribosome such as the messenger RNA (mRNA) entry pore, the translation factor‐binding site and the exit of the ribosomal tunnel. The latter is binding site for both chaperones and complexes associated with protein transport through membranes. Furthermore, the contribution of ribosomal proteins is essential for the assembly and optimal functioning of the ribosome. Key Concepts A universal nomenclature for the ribosomal proteins was introduced in 2014, which terminates the babylonic chaos of the various nomenclature systems. About two thirds of the bacterial ribosomal proteins have counterparts in archaeal and eukaryotic ribosomes. Both rRNA and ribosomal proteins are essential for assembly, structure and function of the ribosomes. A few ribosomal proteins are essential for the assembly, but lack a function in the mature ribosome. In addition to rRNA‐dominated functional hot‐spots such as the decoding centre and the peptidyl‐transferase centre, there are also protein‐dominated functional hot‐spots such as the entry pore for the mRNA on the 30S subunit, the docking site for G‐protein factors and the exit of the tunnel harbouring the nascent peptide chain.

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Die Aufklärung der Ribosomenstruktur (Nobel‐Aufsatz)

Ramakrishnan

2010

Angewandte Chemie

Self Cite

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Ich sage oft zum Scherz, dass ich auch in Madison hätte geboren werden können und dann womöglich Präsident der Vereinigten Staaten geworden wäre. Tatsächlich sah ich meinen Vater das erste Mal, als ich ungefähr sechs Monate alt war. Meine Mutter, R. Rajalakshmi, war Dozentin an der Annamalai University in Chidambaram, und tagsüber küm-merten sich Tanten und Großeltern um mich, wie es bei indischen Großfamilien typisch ist. Als ich ungefähr eineinhalb Jahre alt war, gingen meine Eltern nach Ottawa, wo mein Vater mit einem Stipendium des National Research Council forschte. Sie kehrten nach etwas mehr als einem Jahr wieder zurück, und während ihrer Abwesenheit wurde ich von meiner Großmutter und meiner Tante Gomathi, der ich bis heute sehr nahestehe, erzogen.Als ich drei war zogen meine Eltern nach Baroda (heute besser unter dem gujaratischen Namen Vadodara bekannt, der auf das häufige Vorkommen von Banyanbäumen anspielt), wo meinem Vater in ungewöhnlich jungem Alter die Leitung der neuen Abteilung für Biochemie an der Maharaja Sayajirao University übertragen wurde. Die Abteilung bestand anfangs aus nichts als den bloßen Räumlichkeiten, und weder Personal noch Ausrüstung waren vorhanden. Mein Vater kaufte eine Tischzentrifuge zur Aufreinigung von Enzymen, wobei er Eis aus einer nahegelegenen Eisfabrik beschaffte, um damit die Zentrifuge zu kühlen und die empfindlichen Enzyme während der Prozedur kalt zu halten. Mit diesem Instrumentarium schaffte er es, kurz hintereinander zwei Paper in Nature zu veröffentlichen. Schon bald nach Beginn des Projekts kamen mir wieder Gedanken wegen der Fördermittel. Ich konnte mir nur zu gut vorstellen, was mit einem Antrag an die NIH passieren würde, in dem stand, dass wir keine guten Kristalle der 30S-Untereinheit hatten, aber einige Ideen, wie wir diese bekommen könnten, und wir außerdem auch Ideen über die 50S-Untereinheit hatten, obwohl eine andere Gruppe schon seit fast einem Jahrzehnt an guten Kristallen arbeitete. Da ich selbst schon als Gutachter tätig war, konnte ich mir ausmalen, wie man über meinem Antrag in Gelächter ausbrechen würde. Auf der anderen Seite wusste ich, dass das LMB, wo ich mein Sabbatical verbracht hatte, eine lange Tradition in der Förderung genau dieser Art schwieriger, aber fundamental wichtiger Projekte pflegte. Darüber hinaus könnte ich auf weltweit führende Expertise in kristallographischen Methoden zurückgreifen, falls es technische Probleme gäbe.Also schrieb ich erneut Richard Henderson, der mittlerweile der Direktor des LMB war, und wir vereinbarten ein Treffen am Rande einer Ribosomen-Konferenz in Stockholm, zu der ich ohnehin unterwegs war. Nach meinem Vortrag, den ich über ribosomale Proteine hielt, unterhielt ich mich für ein paar Stunden mit Richard und Tony Crowther (der gemeinsam mit Richard die Abteilung leitete) über das "RibosomenProblem". Sie waren an meinen Ideen interessiert, wollten wissen, wie es mit der Konkurrenzsituation auf dem Gebiet aussah, welche Ansätze fehlgeschlagen waren, welche Auflösung man erreichen musste, um einen me...

show abstract

Crystal Structures of the Ribosome in Complex with Release Factors RF1 and RF2 Bound to a Cognate Stop Codon

Cited by 237 publications

References 58 publications

Accommodating the bacterial decoding release factor as an alien protein among the RNAs at the active site of the ribosome

Accommodating the bacterial decoding release factor as an alien protein among the RNAs at the active site of the ribosome

Ribosomal Proteins: Role in Ribosomal Functions

Die Aufklärung der Ribosomenstruktur (Nobel‐Aufsatz)

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