Structure of BipA in GTP form bound to the ratcheted ribosome

Kumar, Veerendra; Chen, Yun; Ero, Rya; Ahmed, Tofayel; Tan, Jackie; Li, Zhe; Wong, Andrew Barnabas; Bhushan, Shashi; Gao, Yong‐Gui

doi:10.1073/pnas.1513216112

Cited by 36 publications

(71 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Structures of various trGTPases (including EF-G, RF3, TetM, BipA, and LepA) bound to the ribosome provide evidence that these factors all bind similarly, with domains G and II contacting the LSU and SSU, respectively (25)(26)(27)(28)(29). The GTPase activity of trGTPases, including LepA (19), is most greatly stimulated by 70S ribosomes.…”

Section: Discussionmentioning

confidence: 97%

Conserved GTPase LepA (Elongation Factor 4) functions in biogenesis of the 30S subunit of the 70S ribosome

Gibbs

Moon

Chen

et al. 2017

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

View full text Add to dashboard Cite

The physiological role of LepA, a paralog of EF-G found in all bacteria, has been a mystery for decades. Here, we show that LepA functions in ribosome biogenesis. In cells lacking LepA, immature 30S particles accumulate. Four proteins are specifically underrepresented in these particles—S3, S10, S14, and S21—all of which bind late in the assembly process and contribute to the folding of the 3′ domain of 16S rRNA. Processing of 16S rRNA is also delayed in the mutant strain, as indicated by increased levels of precursor 17S rRNA in assembly intermediates. MutationΔlepAconfers a synthetic growth phenotype in absence of RsgA, another GTPase, well known to act in 30S subunit assembly. Analysis of theΔrsgAstrain reveals accumulation of intermediates that resemble those seen in the absence of LepA. These data suggest that RsgA and LepA play partially redundant roles to ensure efficient 30S assembly.

show abstract

Section: Discussionmentioning

confidence: 97%

Conserved GTPase LepA (Elongation Factor 4) functions in biogenesis of the 30S subunit of the 70S ribosome

Gibbs

Moon

Chen

et al. 2017

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

View full text Add to dashboard Cite

show abstract

“…GTPase Activation Site of the Ribosome-bound EF4 -EF4 and BipA are both paralogs of EF-G, and these three proteins share significant structural similarity (9). Interestingly, large conformational changes have been shown to occur in both EF-G (20) and BipA (9) upon binding to the ribosome.…”

Section: Structure Of the Ribosome-ef4-gdpcp Complexmentioning

confidence: 99%

“…Although EF4 lacks the G' subdomain insertion as well as domain IV of EF-G, it has an additional C-terminal domain (CTD). The additional CTD is a feature that is only observed in two trGTPase families, EF4 and BipA; however, their structures are not only different from one another but also represent entirely novel folds (8,9).…”

mentioning

confidence: 99%

Structure of the GTP Form of Elongation Factor 4 (EF4) Bound to the Ribosome

Kumar

Ero

Ahmed

et al. 2016

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Elongation factor 4 (EF4) is a member of the family of ribosome-dependent translational GTPase factors, along with elongation factor G and BPI-inducible protein A. Although EF4 is highly conserved in bacterial, mitochondrial, and chloroplast genomes, its exact biological function remains controversial. Here we present the cryo-EM reconstitution of the GTP form of EF4 bound to the ribosome with P and E site tRNAs at 3.8-Å resolution. Interestingly, our structure reveals an unrotated ribosome rather than a clockwise-rotated ribosome, as observed in the presence of EF4-GDP and P site tRNA. In addition, we also observed a counterclockwise-rotated form of the above complex at 5.7-Å resolution. Taken together, our results shed light on the interactions formed between EF4, the ribosome, and the P site tRNA and illuminate the GTPase activation mechanism at previously unresolved detail.In all cells, proteins are synthesized based on mRNA templates via charged tRNAs by large macromolecular RNA-protein assemblies called ribosomes. Ribosomes harbor three tRNA binding sites, A (aminoacyl tRNA), 2 P (peptidyl tRNA), and E (exiting tRNA) sites, and oscillate between two main states during the peptide chain elongation process, the pretranslocation (PRE) and post-translocation (POST) states, with tRNAs bound to either the A and P or P and E sites, respectively.

show abstract

“…The additional CTD is a structural feature observed only in BipA and EF4 trGTPase families 46,48 . The CTDs of EF4 and BipA are unique having folds that lack similarity to one another as well as to other known proteins 46,48 . The CTD of EF4 comprises one long α-helix cradled by 4 short strands of β-sheet 48 (Fig.…”

Section: Structural Comparison Of Isolated Ef-g Ef4 and Bipamentioning

confidence: 99%

“…1B). The CTD of BipA consists of 2 crossed β-sheets (comprising 2 and 4 β-strands, respectively) wrapped by 3 short α-helices forming a nearly equilateral triangle 46,49 (Fig. 1B).…”

Section: Structural Comparison Of Isolated Ef-g Ef4 and Bipamentioning

confidence: 99%

Similarity and diversity of translational GTPase factors EF-G, EF4, and BipA: From structure to function

et al. 2016

Self Cite

View full text Add to dashboard Cite

EF-G, EF4, and BipA are members of the translation factor family of GTPases with a common ribosome binding mode and GTPase activation mechanism. However, topological variations of shared as well as unique domains ensure different roles played by these proteins during translation. Recent X-ray crystallography and cryo-electron microscopy studies have revealed the structural basis for the involvement of EF-G domain IV in securing the movement of tRNAs and mRNA during translocation as well as revealing how the unique C-terminal domains of EF4 and BipA interact with the ribosome and tRNAs contributing to the regulation of translation under certain conditions. EF-G, EF-4, and BipA are intriguing examples of structural variations on a common theme that results in diverse behavior and function. Structural studies of translational GTPase factors have been greatly facilitated by the use of antibiotics, which have revealed their mechanism of action.

show abstract

Structure of BipA in GTP form bound to the ratcheted ribosome

Cited by 36 publications

References 51 publications

Conserved GTPase LepA (Elongation Factor 4) functions in biogenesis of the 30S subunit of the 70S ribosome

Conserved GTPase LepA (Elongation Factor 4) functions in biogenesis of the 30S subunit of the 70S ribosome

Structure of the GTP Form of Elongation Factor 4 (EF4) Bound to the Ribosome

Similarity and diversity of translational GTPase factors EF-G, EF4, and BipA: From structure to function

Contact Info

Product

Resources

About