Protein folding: Understanding the role of water and the low Reynolds number environment as the peptide chain emerges from the ribosome and folds

Sen, Siddhartha; Voorheis, H. Paul

doi:10.1016/j.jtbi.2014.07.025

Cited by 13 publications

(10 citation statements)

References 60 publications

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“…The presence of a minimum number of closely spaced hydrophobic residues, from six to seven, is sufficient to induce cotranslational long-distance folding initiated by hydrophobic collapse in the absence of externally applied forces (14). Thus, the sequence positions where compaction is likely to take place depend on the number of hydrophobic residues along the sequence and their corresponding hydrophobicity, as well as the relative distances between them.…”

Section: Resultsmentioning

confidence: 99%

“…Thus, the sequence positions where compaction is likely to take place depend on the number of hydrophobic residues along the sequence and their corresponding hydrophobicity, as well as the relative distances between them. The likelihood of cotranslational folding for a given sequence stretch can be expressed as the sequence-dependent hydrophobic collapse index (HCI) (SI Appendix) (14). The magnitude of the applied force on the growing nascent chain also influences cotranslational nascent chain compaction due to folding.…”

Section: Resultsmentioning

confidence: 99%

“…These ensemble studies confirm that larger proteins collapse fast into a polyglobular conformation, fold through native-like intermediates in a distinct pathway, and emerge slowly as native structures (11,12). With a few exceptions, stable tertiary structure formation requires the presence of hydrophobic amino acids (13,14).…”

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confidence: 75%

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Translation and folding of single proteins in real time

Wruck

Katranidis

Nierhaus

et al. 2017

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

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Protein biosynthesis is inherently coupled to cotranslational protein folding. Folding of the nascent chain already occurs during synthesis and is mediated by spatial constraints imposed by the ribosomal exit tunnel as well as self-interactions. The polypeptide's vectorial emergence from the ribosomal tunnel establishes the possible folding pathways leading to its native tertiary structure. How cotranslational protein folding and the rate of synthesis are linked to a protein's amino acid sequence is still not well defined. Here, we follow synthesis by individual ribosomes using dual-trap optical tweezers and observe simultaneous folding of the nascent polypeptide chain in real time. We show that observed stalling during translation correlates with slowed peptide bond formation at successive proline sequence positions and electrostatic interactions between positively charged amino acids and the ribosomal tunnel. We also determine possible cotranslational folding sites initiated by hydrophobic collapse for an unstructured and two globular proteins while directly measuring initial cotranslational folding forces. Our study elucidates the intricate relationship among a protein's amino acid sequence, its cotranslational nascent-chain elongation rate, and folding.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Translation and folding of single proteins in real time

Wruck

Katranidis

Nierhaus

et al. 2017

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

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“…Recently it was demonstrated that water plays a crucial role in this process as it forms hydrogen bonds with the amino acid chains, facilitating their collapse into three dimensional molecular structures. In the presence of water, folding occurs almost instantly (140 ns), resulting in biologically active molecules available for chemical reactions at the opportune time (Sen and Voorheis, 2014 ; Vajda and Perczel, 2014 ). In the absence of hydration the folding process is significantly slower and the biomolecules may miss the timing of their reactions.…”

Section: Water and Protein Misfolding Disordersmentioning

confidence: 99%

Dehydration and Cognition in Geriatrics: A Hydromolecular Hypothesis

Sfera

Cummings

Osorio

2016

Front. Mol. Biosci.

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Dehydration is one of the ten most frequent diagnoses responsible for the hospital admission of elderly in the United States. It is associated with increased mortality, morbidity and an estimated cost of 1.14 billion per year (Xiao et al., 2004; Schlanger et al., 2010; Pretorius et al., 2013; Frangeskou et al., 2015). Older individuals are predisposed to dehydration encephalopathy as a result of decreased total body water (TBW) and diminished sensation of thirst. We hypothesize that thirst blunting in older individuals is the result of a defective microRNA-6842-3p failing to silence the expression of the vesicular GABA transporters (VGAT) and alpha 7 cholinergic nicotinic receptors in the subfornical organ (SFO) of the hypothalamus. We hypothesize further that resultant dehydration facilitates protein misfolding and aggregation, predisposing to neurocognitive disorders. We completed a search of predicted microRNA targets, utilizing the public domain tool miRDB and found that microRNA-6842-3p modulates the SLC6A1 and CHRNA7 genes both of which were previously hypothesized to inhibit the thirst sensation by their action on SFO. The primary aim of this article is to answer two questions: Can prevention and correction of dehydration in elderly lower age-related cognitive deterioration? Can exosomal miR-6842 in the peripheral blood predict dehydration encephalopathy in elderly?

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“…Water is a ubiquitous liquid known for its important role in different biological, chemical, and atmospheric processes . Its role in protein folding and their stability has been well documented . Liquid water, in which the monomers are connected through directional hydrogen bonded (H‐bond) network resulting in a high degree of structure, is the most studied liquid .…”

Section: Introductionmentioning

confidence: 99%

Investigation of solvation of ammonium salts: A Raman spectroscopy and ab initio study

Mukhopadhyay

Dubey

2017

J Raman Spectroscopy

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The effect of dissolved salts on the hydrogen bonded network in water is extremely important to be understood, as it plays an important role in many aspects of structure and dynamics in aqueous solutions. We have undertaken a study of this phenomenon, using NH4Cl (AC) and (NH4)2SO4 (AS), as the salts for influencing the hydrogen bonded network in water. The effects of varying the temperature and concentration in these aqueous solutions of both the salts, on the Raman spectra were studied, over the wavenumber range 50–4000 cm−1. It was found that at 25 °C, with increasing AS concentration, a monotonic increase in intensity of spectral features on the low wavenumber side (~3200 cm−1 region) of the O–H stretching band was observed, whereas AC showed the opposite effect. A parameter (χstruct) is defined from the spectral data, which indicates that more hydrogen bonded network forms in presence of AS salt compared with AC salt, in aqueous solution. Temperature variation study also reveals that, presence of AC induces a more disordered network in aqueous solutions, than AS. To support these conclusions, we have performed ab initio calculation for the salt⋯nW species, where n = 1−8, using the MP2/6–31+G(d,p) level of theory. Solvent separated ion pair formation has been reported for NH4+ and Cl− ions, whereas NH4+ and SO42− ions remain as contact ion pair up to AS⋯8W cluster. This study helps understand the effect of salt water interaction at the molecular level and may have huge implications in atmospheric physics, geophysics, and ice crystallization.

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Protein folding: Understanding the role of water and the low Reynolds number environment as the peptide chain emerges from the ribosome and folds

Cited by 13 publications

References 60 publications

Translation and folding of single proteins in real time

Translation and folding of single proteins in real time

Dehydration and Cognition in Geriatrics: A Hydromolecular Hypothesis

Investigation of solvation of ammonium salts: A Raman spectroscopy and ab initio study

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