ArticlePloS one2014
Preventing disulfide bond formation weakens non-covalent forces among lysozyme aggregates.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 18 citations in OpenAlex.
- Mechanism of Reduced Glutathione Induced Lysozyme Defolding and Molecular Self-Assembly.Foods (Basel, Switzerland) · 2023Article
- Insights on Aggregation of Hen Egg-White Lysozyme from Raman Spectroscopy and MD Simulations.Molecules (Basel, Switzerland) · 2022Article
- Freeze-thaw characterization process to minimize aggregation and enable drug product manufacturing of protein based therapeutics.Scientific reports · 2021Article
- The acidic tail of HMGB1 regulates its secondary structure and conformational flexibility: A circular dichroism and molecular dynamics simulation study.Computational and structural biotechnology journal · 2020Article
- The extreme hyper-reactivity of Cys94 in lysozyme avoids its amorphous aggregation.Scientific reports · 2018Article
- The Native Monomer of Bacillus Pumilus Ribonuclease Does Not Exist Extracellularly.BioMed research international · 2018Article
- Hydrogen sulfide inhibits amyloid formation.The journal of physical chemistry. B · 2015Article
- On the characterization of intermediates in the isodesmic aggregation pathway of hen lysozyme at alkaline pH.PloS one · 2014Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nonnative disulfide bonds have been observed among protein aggregates in several diseases like amyotrophic lateral sclerosis, cataract and so on. The molecular mechanism by which formation of such bonds promotes protein aggregation is poorly understood. Here in this work we employ previously well characterized aggregation of hen eggwhite lysozyme (HEWL) at alkaline pH to dissect the molecular role of nonnative disulfide bonds on growth of HEWL aggregates. We employed time-resolved fluorescence anisotropy, atomic force microscopy and single-molecule force spectroscopy to quantify the size, morphology and non-covalent interaction forces among the aggregates, respectively. These measurements were performed under conditions when disulfide bond formation was allowed (control) and alternatively when it was prevented by alkylation of free thiols using iodoacetamide. Blocking disulfide bond formation affected growth but not growth kinetics of aggregates which were ∼50% reduced in volume, flatter in vertical dimension and non-fibrillar in comparison to control. Interestingly, single-molecule force spectroscopy data revealed that preventing disulfide bond formation weakened the non-covalent interaction forces among monomers in the aggregate by at least ten fold, thereby stalling their growth and yielding smaller aggregates in comparison to control. We conclude that while constrained protein chain dynamics in correctly disulfide bonded amyloidogenic proteins may protect them from venturing into partial folded conformations that can trigger entry into aggregation pathways, aberrant disulfide bonds in non-amyloidogenic proteins (like HEWL) on the other hand, may strengthen non-covalent intermolecular forces among monomers and promote their aggregation.
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