Folding zones inside the ribosomal exit tunnel

Lu, Jianjun; Deutsch, Carol

doi:10.1038/nsmb1021

Cited by 238 publications

(249 citation statements)

References 33 publications

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“…When peptidyl-tRNA 2 Gly is formed, the length of the nascent peptide is about 20 amino acids, placing the exchanged residues in the middle part of the peptide exit tunnel, beyond the constriction formed by ribosomal proteins L4 and L22 (ref. 19). Although it is difficult to predict the exact location of the nascent peptide 14-30 region in the tunnel, we tested whether mutations of the proteins L4 and L22, as well as of ribosomal protein L23, which resides at the tunnel exit and is involved in signalling from inside the tunnel to the outside 20 , affect bypassing.…”

Section: Resultsmentioning

confidence: 99%

High-efficiency translational bypassing of non-coding nucleotides specified by mRNA structure and nascent peptide

et al. 2014

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The gene product 60 (gp60) of bacteriophage T4 is synthesized as a single polypeptide chain from a discontinuous reading frame as a result of bypassing of a non-coding mRNA region of 50 nucleotides by the ribosome. To identify the minimum set of signals required for bypassing, we recapitulated efficient translational bypassing in an in vitro reconstituted translation system from Escherichia coli. We find that the signals, which promote efficient and accurate bypassing, are specified by the gene 60 mRNA sequence. Systematic analysis of the mRNA suggests unexpected contributions of sequences upstream and downstream of the non-coding gap region as well as of the nascent peptide. During bypassing, ribosomes glide forward on the mRNA track in a processive way. Gliding may have a role not only for gp60 synthesis, but also during regular mRNA translation for reading frame selection during initiation or tRNA translocation during elongation.

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Section: Resultsmentioning

confidence: 99%

High-efficiency translational bypassing of non-coding nucleotides specified by mRNA structure and nascent peptide

et al. 2014

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“…Lu and Deutsch [53] found that helix formation is promoted at the wider portions of the exit tunnel. Experimental and theoretical studies aimed at untangling possible contributions from entropy reduction by confinement, surface interaction, and modulation of water activity will shed light on the functional roles of the ribosomal exit tunnel in the folding of nascent proteins.…”

Section: Protein Folding In Cellular Environmentsmentioning

confidence: 99%

Protein folding in confined and crowded environments

Zhou

2008

Archives of Biochemistry and Biophysics

148

137

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Confinement and crowding are two major factors that can potentially impact protein folding in cellular environments. Theories based on considerations of excluded volumes predict disparate effects on protein folding stability for confinement and crowding: confinement can stabilize proteins by over 10k B T but crowding has a very modest effect on stability. On the other hand, confinement and crowding are both predicted to favor conformations of the unfolded state which are compact, and consequently may increase the folding rate. These predictions are largely borne out by experimental studies of protein folding under confined and crowded conditions in the test tube. Protein folding in cellular environments is further complicated by interactions with surrounding surfaces and other factors. Concerted theoretical modeling and test-tube and in vivo experiments promise to elucidate the complexity of protein folding in cellular environments.The complexity of the cellular environments in which proteins function is increasingly been appreciated [1]. Potential impacts of two related, but distinct factors, confinement and macromolecular crowding, on protein folding are receiving extensive attention [2][3][4][5]. Confinement arises from encapsulation of proteins in compartments with dimensions on the scales of 10's to 100's Å, which are only moderately larger than the sizes of the proteins themselves. Examples of such compartments include the Anfinsen cage of chaperonins and the exit tunnel of ribosomes. Crowding refers to the exclusion of volumes to proteins of interest by the presence of other macromolecules. The aims of this paper are to discuss potential impacts of confinement and crowding on protein folding and to review the progress made by recent studies on protein folding in confined and crowded conditions and in cellular environments.

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“…While the folding of small protein modules has been studied in great detail by in vitro experiments, how de novo folding is coordinated with translation is not yet well understood (1,2). It is generally thought that nascent polypeptide chains emerging from the ribosome must be maintained by molecular chaperones in a non-aggregated, folding-competent state, at least until a complete domain capable of independent folding has been made available (3)(4)(5). A major function of chaperones that interact with nascent chains is to shield exposed hydrophobic amino acid residues that can give rise to aggregation in the highly crowded environment of the cytosol.…”

mentioning

confidence: 99%

Versatility of Trigger Factor Interactions with Ribosome-Nascent Chain Complexes

Lakshmipathy

Gupta²,

Pinkert

et al. 2010

Journal of Biological Chemistry

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Trigger factor (TF) is the first molecular chaperone that interacts with nascent chains emerging from bacterial ribosomes. TF is a modular protein, consisting of an N-terminal ribosome binding domain, a PPIase domain, and a C-terminal domain, all of which participate in polypeptide binding. To directly monitor the interactions of TF with nascent polypeptide chains, TF variants were site-specifically labeled with an environmentally sensitive NBD fluorophore. We found a marked increase in TF-NBD fluorescence during translation of firefly luciferase (Luc) chains, which expose substantial regions of hydrophobicity, but not with nascent chains lacking extensive hydrophobic segments. TF remained associated with Luc nascent chains for 111 ؎ 7 s, much longer than it remained bound to the ribosomes (t1 ⁄ 2 ϳ 10 -14 s). Thus, multiple TF molecules can bind per nascent chain during translation. The Escherichia coli cytosolic proteome was classified into predicted weak and strong interactors for TF, based on the occurrence of continuous hydrophobic segments in the primary sequence. The residence time of TF on the nascent chain generally correlated with the presence of hydrophobic regions and the capacity of nascent chains to bury hydrophobicity. Interestingly, TF bound the signal sequence of a secretory protein, pOmpA, but not the hydrophobic signal anchor sequence of the inner membrane protein FtsQ. On the other hand, proteins lacking linear hydrophobic segments also recruited TF, suggesting that TF can recognize hydrophobic surface features discontinuous in sequence. Moreover, TF retained significant affinity for the folded domain of the positively charged, ribosomal protein S7, indicative of an alternative mode of TF action. Thus, unlike other chaperones, TF appears to employ multiple mechanisms to interact with a wide range of substrate proteins.

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Folding zones inside the ribosomal exit tunnel

Cited by 238 publications

References 33 publications

High-efficiency translational bypassing of non-coding nucleotides specified by mRNA structure and nascent peptide

High-efficiency translational bypassing of non-coding nucleotides specified by mRNA structure and nascent peptide

Protein folding in confined and crowded environments

Versatility of Trigger Factor Interactions with Ribosome-Nascent Chain Complexes

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