Small protein domains fold inside the ribosome exit tunnel

Marino, Jacopo; Heijne, Gunnar von; Beckmann, Roland

doi:10.1002/1873-3468.12098

Cited by 76 publications

(93 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The linker is composed of 17 residues (130–146) that form two consecutive turns: one connecting the C-terminal α-helix which is a canonical α-turn (I140–K144), followed by a less well-ordered turn without hydrogen bonding (Figure 2a–d and Video 2). Protein folding events have been demonstrated to occur within the ribosomal exit tunnel (Holtkamp et al, 2015; Lin et al, 2012; Marino et al, 2016; Nilsson et al, 2015; Tu et al, 2014); (Bhushan et al, 2010b; Matheisl et al, 2015); Of those so far characterized, folding was shown to occur within the lower region of the tunnel, e.g. ADR1 (Nilsson et al, 2015) and within the vestibule at the periphery where the exit tunnel widens (Cabrita et al, 2016; Nilsson et al, 2017; Trovato and O'Brien, 2016; Tu et al, 2014).…”

Section: Resultsmentioning

confidence: 99%

The force-sensing peptide VemP employs extreme compaction and secondary structure formation to induce ribosomal stalling

Cheng

Sohmen

et al. 2017

eLife

Self Cite

113

View full text Add to dashboard Cite

Interaction between the nascent polypeptide chain and the ribosomal exit tunnel can modulate the rate of translation and induce translational arrest to regulate expression of downstream genes. The ribosomal tunnel also provides a protected environment for initial protein folding events. Here, we present a 2.9 Å cryo-electron microscopy structure of a ribosome stalled during translation of the extremely compacted VemP nascent chain. The nascent chain forms two α-helices connected by an α-turn and a loop, enabling a total of 37 amino acids to be observed within the first 50–55 Å of the exit tunnel. The structure reveals how α-helix formation directly within the peptidyltransferase center of the ribosome interferes with aminoacyl-tRNA accommodation, suggesting that during canonical translation, a major role of the exit tunnel is to prevent excessive secondary structure formation that can interfere with the peptidyltransferase activity of the ribosome.DOI: http://dx.doi.org/10.7554/eLife.25642.001

show abstract

Section: Resultsmentioning

confidence: 99%

The force-sensing peptide VemP employs extreme compaction and secondary structure formation to induce ribosomal stalling

Cheng

Sohmen

et al. 2017

eLife

Self Cite

113

View full text Add to dashboard Cite

show abstract

“…The narrowness and length of the exit tunnel (~20x100 Å) significantly constrains the most C-terminal residues of the nascent polypeptide chain to a small range of mostly extended or α-helical conformations [6,7]. The formation of bulky tertiary structure does not begin until the nascent chain is long enough to emerge from the exit tunnel (>35 aa), although there is evidence that the broader ‘vestibule’ near the end of the tunnel is wide enough to enable the nascent chain to fold back on itself to make some local tertiary structure contacts [8,9]. Synonymous codon substitutions near the 5′ end of a coding sequence are therefore unlikely to affect co-translational protein folding, as very little of the nascent chain has been translated and the portion that has been synthesized is constrained within the tunnel.…”

Section: Ribosome Structure and The Logistics Of Co-translational Promentioning

confidence: 99%

Quality over quantity: optimizing co-translational protein folding with non-‘optimal’ synonymous codons

Jacobson

Clark

2016

Current Opinion in Structural Biology

View full text Add to dashboard Cite

Protein folding occurs on a time scale similar to peptide bond formation by the ribosome, which has long sparked speculation that altering translation rate could alter the folding mechanism or even the final folded structure of a protein in vivo. Recent results have provided strong support for this model: synonymous substitutions to codons with different usage frequency, which are often translated at different rates, have been shown to significantly alter the co-translational folding mechanism of some proteins, leading to altered cell function. Here we review recent progress towards understanding the connections between synonymous codon usage, translation rate and co-translational protein folding mechanisms.

show abstract

“…However, in the recent years many studies have shown in eukaryotes as well as in prokaryotes that protein folding already begins on the ribosome, while the C-terminal part of the polypeptide is still in the process of being extended at the peptidyl-transferase center. Furthermore, several recent studies have shown that the formation of secondary structures, such as α-helices, already begins within the ribosomal exit tunnel [8][9][10][11][12][13][14][15].…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Dynamic Behavior of Trigger Factor on the Ribosome

Deeng

Chan

Sluis

et al. 2016

Journal of Molecular Biology

View full text Add to dashboard Cite

Trigger factor (TF) is the only ribosome-associated chaperone in bacteria. It interacts with hydrophobic segments in nascent chain (NCs) as they emerge from the ribosome. TF binds via its N-terminal ribosome-binding domain (RBD) mainly to ribosomal protein uL23 at the tunnel exit on the large ribosomal subunit. Whereas earlier structural data suggested that TF binds as a rigid molecule to the ribosome, recent comparisons of structural data on substrate-bound, ribosome-bound, and TF in solution from different species suggest that this chaperone is a rather flexible molecule. Here, we present two cryo-electron microscopy structures of TF bound to ribosomes translating an mRNA coding for a known TF substrate from Escherichia coli of a different length. The structures reveal distinct degrees of flexibility for the different TF domains, a conformational rearrangement of the RBD upon ribosome binding, and an increase in rigidity within TF when the NC is extended. Molecular dynamics simulations agree with these data and offer a molecular basis for these observations.

show abstract

Small protein domains fold inside the ribosome exit tunnel

Cited by 76 publications

References 22 publications

The force-sensing peptide VemP employs extreme compaction and secondary structure formation to induce ribosomal stalling

The force-sensing peptide VemP employs extreme compaction and secondary structure formation to induce ribosomal stalling

Quality over quantity: optimizing co-translational protein folding with non-‘optimal’ synonymous codons

Dynamic Behavior of Trigger Factor on the Ribosome

Contact Info

Product

Resources

About