Cysteine oxidation and disulfide formation in the ribosomal exit tunnel

Schulte, Linda; Mao, Jiafei; Reitz, Julian; Sreeramulu, Sridhar; Kudlinzki, D.; Hodirnau, Victor-Valentin; Meier-Credo, Jakob; Saxena, Krishna; Buhr, Florian; Langer, Julian D.; Blackledge, Martin; Frangakis, Achilleas S.; Glaubitz, Clemens; Schwalbe, Harald

doi:10.1038/s41467-020-19372-x

Cited by 36 publications

(37 citation statements)

References 66 publications

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“…Enhancements of up to 150-fold have been reported on complex systems such as GPCRs (Joedicke et al, 2018) or ribosome nascent chain complexes (Schulte et al, 2020). This significant boost in sensitivity can be highly beneficial for real-time NMR applications.…”

Section: Dnpmentioning

confidence: 99%

Real-time NMR spectroscopy in the study of biomolecular kinetics and dynamics

Pintér

Hohmann

Grün

et al. 2021

Preprint

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Abstract. The review describes the application of NMR spectroscopy to study kinetics of folding, refolding and aggregation of proteins, RNA and DNA. Time-resolved NMR experiments can be conducted in a reversible or an irreversible manner. In particular irreversible folding experiments pose large requirements on (i) the signal-to-noise due to the time limitations and (ii) on synchronizing the refolding steps. Thus, this contribution discusses the application of methods for signal-to-noise increases including dynamic nuclear polarization, hyperpolarization and photo-CIDNP for the study of time-resolved NMR studies. Further, methods are reviewed ranging from pressure- and temperature-jump, light induction and rapid mixing to induce rapidly non-equilibrium conditions required to initiate folding.

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Section: Dnpmentioning

confidence: 99%

Real-time NMR spectroscopy in the study of biomolecular kinetics and dynamics

Pintér

Hohmann

Grün

et al. 2021

Preprint

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“…Biomacromolecules can be unfolded in many different ways (Fürtig et al, 2007b;Roder et al, 2004). Proteins can be chemically denatured using high concentrations (6-8 M) of guanidinium chloride (GdnCl) (Logan et al, 1994;Zeeb and Balbach, 2004) or urea (Egan et al, 1993;Neri et al, 1992;Schwalbe et al, 1997), but also organic solvents including 2,2,2-triflouroethanol (TFE) or dimethyl sulfoxide (DMSO) (Buck, 1998;Buck et al, 1995Buck et al, , 1993Nishimura et al, 2005). The (re-)folding of chemically denatured proteins can then be initiated with a rapid dilution into native buffer conditions (Balbach et al, 1995) or vice versa for unfolding of native proteins (Kiefhaber et al, 1995).…”

Section: Rapid Mixingmentioning

confidence: 99%

Real-time nuclear magnetic resonance spectroscopy in the study of biomolecular kinetics and dynamics

et al. 2021

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Abstract. The review describes the application of nuclear magnetic resonance (NMR) spectroscopy to study kinetics of folding, refolding and aggregation of proteins, RNA and DNA. Time-resolved NMR experiments can be conducted in a reversible or an irreversible manner. In particular, irreversible folding experiments pose large requirements for (i) signal-to-noise due to the time limitations and (ii) synchronising of the refolding steps. Thus, this contribution discusses the application of methods for signal-to-noise increases, including dynamic nuclear polarisation, hyperpolarisation and photo-CIDNP for the study of time-resolved NMR studies. Further, methods are reviewed ranging from pressure and temperature jump, light induction to rapid mixing to induce rapidly non-equilibrium conditions required to initiate folding.

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“…In other research addressing the role of disulfides in influencing the conformational dynamics of proteins, it was found that the introduction of single disulfides spanning a large portion of the lysozyme shifted both the structure and dynamics of hydrophobic core residues of the protein [ 127 ]. In a recent landmark study that utilized a combination of biophysical and computational techniques (mass spectrometry, theoretical simulations, dynamic nuclear polarization-enhanced solid-state nuclear magnetic resonance and cryo-electron microscopy), it was demonstrated that thiol groups of cysteines undergo chemical mutation to form S-glutathionylated and S-nitrosylated adducts and impacted the formation non-native disulfide bonds [ 128 ]. This covalent chemical modification was found to occur prior to chain release, supported by arguments that since the ribosome exit tunnel provides sufficient space even for disulfide bond formation, it is not surprising to detect these chemo-mutated variants.…”

Section: Learnings From Oxidative Protein Foldingmentioning

confidence: 99%

Revisiting the Formation of a Native Disulfide Bond: Consequences for Protein Regeneration and Beyond

Narayan¹

2020

Molecules

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Oxidative protein folding involves the formation of disulfide bonds and the regeneration of native structure (N) from the fully reduced and unfolded protein (R). Oxidative protein folding studies have provided a wealth of information on underlying physico-chemical reactions by which disulfide-bond-containing proteins acquire their catalytically active form. Initially, we review key events underlying oxidative protein folding using bovine pancreatic ribonuclease A (RNase A), bovine pancreatic trypsin inhibitor (BPTI) and hen-egg white lysozyme (HEWL) as model disulfide bond-containing folders and discuss consequential outcomes with regard to their folding trajectories. We re-examine the findings from the same studies to underscore the importance of forming native disulfide bonds and generating a “native-like” structure early on in the oxidative folding pathway. The impact of both these features on the regeneration landscape are highlighted by comparing ideal, albeit hypothetical, regeneration scenarios with those wherein a native-like structure is formed relatively “late” in the R→N trajectory. A special case where the desired characteristics of oxidative folding trajectories can, nevertheless, stall folding is also discussed. The importance of these data from oxidative protein folding studies is projected onto outcomes, including their impact on the regeneration rate, yield, misfolding, misfolded-flux trafficking from the endoplasmic reticulum (ER) to the cytoplasm, and the onset of neurodegenerative disorders.

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Cysteine oxidation and disulfide formation in the ribosomal exit tunnel

Cited by 36 publications

References 66 publications

Real-time NMR spectroscopy in the study of biomolecular kinetics and dynamics

Real-time NMR spectroscopy in the study of biomolecular kinetics and dynamics

Real-time nuclear magnetic resonance spectroscopy in the study of biomolecular kinetics and dynamics

Revisiting the Formation of a Native Disulfide Bond: Consequences for Protein Regeneration and Beyond

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