Ribosomes and ribosomal RNA as chaperones for folding of proteins

Kudlicki, Wiesław; Coffman, Ashley; Kramer, Gisela; Hardesty, Boyd

doi:10.1016/s1359-0278(97)00014-x

Cited by 97 publications

(72 citation statements)

References 38 publications

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“…It has been shown over the past 2 decades that the ribosome is able to refold ϳ20 different proteins in vitro (1)(2)(3)(4)(5). The protein folding activity of the ribosome (PFAR) 4 is not restricted to any particular species or groups of organisms because ribosomes from various sources have been shown to possess this activity (1,2,6).…”

Section: Domain V Of the 23s/25s/28s Rrna Of The Large Ribosomal Subumentioning

confidence: 99%

“…As 6AP has planar structure, which presumably makes it prone to layered stacking between the RNA bases, a detailed understanding of the chemistry of the 6AP-rRNA interaction requires further investigation beyond the scope of this work. 5 Model of Domain V rRNA-assisted Refolding and 6AP Inhibition-We propose a simple model to explain the mechanism of protein folding with domain V rRNA and its inhibition by 6AP (Fig. 7).…”

Section: Variants Of E Colimentioning

confidence: 99%

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The Antiprion Compound 6-Aminophenanthridine Inhibits the Protein Folding Activity of the Ribosome by Direct Competition

Pang

Kurella

Voisset

et al. 2013

Journal of Biological Chemistry

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Background: 6-Aminophenanthridine (6AP) is an inhibitor of the protein folding activity of the ribosome (PFAR). Results: The protein substrates and 6AP bind at common sites on rRNA; mutations at those sites abolish binding and inhibit PFAR. Conclusion: 6AP competitively obstructs the protein-binding sites and thereby inhibits PFAR. Significance: We have clarified the mechanism by which 6AP inhibits PFAR.

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Section: Domain V Of the 23s/25s/28s Rrna Of The Large Ribosomal Subumentioning

confidence: 99%

Section: Variants Of E Colimentioning

confidence: 99%

The Antiprion Compound 6-Aminophenanthridine Inhibits the Protein Folding Activity of the Ribosome by Direct Competition

Pang

Kurella

Voisset

et al. 2013

Journal of Biological Chemistry

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“…␣-Crystallin, which belongs to small heat shock protein (sHSP) family (17), has been proposed to have a micellar architecture (11,12). Even nonprotein biological molecules such as ribosomal RNA (18,19) and phospholipid (20), which can form micelle-type aggregates, were shown to function as molecular chaperones.…”

mentioning

confidence: 99%

Molecular Chaperone-like Properties of an Unfolded Protein, αs-Casein

Bhattacharyya¹,

Das

1999

Journal of Biological Chemistry

177

159

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All molecular chaperones known to date are well organized, folded protein molecules whose three-dimensional structure are believed to play a key role in the mechanism of substrate recognition and subsequent assistance to folding. A common feature of all protein and nonprotein molecular chaperones is the propensity to form aggregates very similar to the micellar aggregates. In this paper we show that ␣ s -casein, abundant in mammalian milk, which has no well defined secondary and tertiary structure but exits in nature as a micellar aggregate, can prevent a variety of unrelated proteins/ enzymes against thermal-, chemical-, or light-induced aggregation. It also prevents aggregation of its natural substrates, the whey proteins. ␣ s -Casein interacts with partially unfolded proteins through its solvent-exposed hydrophobic surfaces. The absence of disulfide bridge or free thiol groups in its sequence plays important role in preventing thermal aggregation of whey proteins caused by thiol-disulfide interchange reactions. Our results indicate that ␣ s -casein not only prevents the formation of huge insoluble aggregates but it can also inhibit accumulation of soluble aggregates of appreciable size. Unlike other molecular chaperones, this protein can solubilize hydrophobically aggregated proteins. This protein seems to have some characteristics of cold shock protein, and its chaperone-like activity increases with decrease of temperature.

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“…Since the ribosomes from all sources possess the PTC, having remarkably similar secondary structures, it is not surprising to find that all the PTCs from different sources have protein synthesizing and folding properties which we and others have observed. [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] At this point, it should be possible to take the PTC out of the large subunit context and check whether it can fold proteins in vitro. That would make it possible to work out the physico-chemical mechanism of this process.…”

Section: Protein Folding: In Vivo To In Vitromentioning

confidence: 99%

Ribosome: The Structure–Function Relation and a New Paradigm to the Protein Folding Problem

Das

Samanta

Das

et al. 2010

Israel Journal of Chemistry

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The rate of protein synthesis is about seven and fifteen amino acids per second, in the eukaryotic and the bacterial ribosome, respectively. Hence, a few minutes is required to synthesize a polypeptide of an average length. This is much longer than the time needed for the hydrophobic collapse (folding) to take place. So a polypeptide gets enough time to form its local secondary to tertiary structures cotranslationally and put such segments in proper order while in association with the ribosome, unless something prevents its entire length from folding. As reported earlier, ribosomes from prokaryotes, eukaryotes, and mitochondria act as molds for protein folding, and each mold has a set of recognition sites for all proteins. More specifically, the mold is the peptidyl transferase center (PTC), a part of the large RNA of the large ribosomal subunit. Specific amino acids from different random coil regions in a protein interact with specific nucleotides in the PTC, which brings the entire length of the protein into the small space of the PTC mold. The mold thus helps to stabilize the entropy‐driven collapsed state of the polypeptide. The process also divides the protein into small segments; each segment is connected at two ends with two nucleotides and can fold in the ribosomal environment. The segments dissociate in such a sequence that the organization proceeds hierarchically from the core of the globular protein radially towards the outer surface. Then the protein dissociates from the ribosome in a “folding competent state” which does the final fine tuning in folding outside the ribosome. While the ribosomal contact and release are over in 1–2 minutes in vitro, the fine tuning takes about 5–10 minutes. Release from the ribosome needs no added energy factor from outside, like ATP.

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Ribosomes and ribosomal RNA as chaperones for folding of proteins

Cited by 97 publications

References 38 publications

The Antiprion Compound 6-Aminophenanthridine Inhibits the Protein Folding Activity of the Ribosome by Direct Competition

The Antiprion Compound 6-Aminophenanthridine Inhibits the Protein Folding Activity of the Ribosome by Direct Competition

Molecular Chaperone-like Properties of an Unfolded Protein, αs-Casein

Ribosome: The Structure–Function Relation and a New Paradigm to the Protein Folding Problem

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