scholarly journals Signatures of the Protein Folding Pathway in Two-Dimensional Ultraviolet Spectroscopy

2014 ◽  
Vol 5 (8) ◽  
pp. 1341-1346 ◽  
Author(s):  
Jun Jiang ◽  
Zaizhi Lai ◽  
Jin Wang ◽  
Shaul Mukamel
Keyword(s):  
Protein Folding ◽  
Folding Pathway ◽  
Ultraviolet Spectroscopy ◽  
Two Dimensional

Two dimensional crowding effects on protein folding at interfaces observed by chiral vibrational sum frequency generation spectroscopy

2018 ◽  
Vol 20 (35) ◽  
pp. 22421-22426 ◽  
Author(s):  
Wei Liu ◽  
Li Fu ◽  
Zhuguang Wang ◽  
Zahra Sohrabpour ◽  
Xiaobai Li ◽  
...  
Keyword(s):  
Protein Folding ◽  
Sum Frequency Generation ◽  
Molecular Crowding ◽  
Two Dimensional ◽  
Sum Frequency ◽  
Crowding Effects ◽  
Sum Frequency Generation Spectroscopy ◽  
Frequency Generation

Vibrational sum frequency generation studies demonstrate the effects of two-dimensional molecular crowding on protein folding at interfaces.

scholarly journals Thermosensitive PBP2a requires extracellular folding factors PrsA and HtrA1 for Staphylococcus aureus MRSA β-lactam resistance

2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Mélanie Roch ◽  
Emmanuelle Lelong ◽  
Olesya O. Panasenko ◽  
Roberto Sierra ◽  
Adriana Renzoni ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Protein Folding ◽  
Antibiotic Resistance ◽  
Active Site ◽  
Complete Loss ◽  
Folding Pathway ◽  
Human Pathogen ◽  
Clinical Challenge ◽  
Aggregation Activity ◽  
Horizontal Acquisition

AbstractStaphylococcus aureus is a major human pathogen and represents a clinical challenge because of widespread antibiotic resistance. Methicillin resistant Staphylococcus aureus (MRSA) is particularly problematic and originates by the horizontal acquisition of mecA encoding PBP2a, an extracellular membrane anchored transpeptidase, which confers resistance to β-lactam antibiotics by allosteric gating of its active site channel. Herein, we show that dual disruption of PrsA, a lipoprotein chaperone displaying anti-aggregation activity, together with HtrA1, a membrane anchored chaperone/serine protease, resulted in severe and synergistic attenuation of PBP2a folding that restores sensitivity to β-lactams such as oxacillin. Purified PBP2a has a pronounced unfolding transition initiating at physiological temperatures that leads to irreversible precipitation and complete loss of activity. The concordance of genetic and biochemical data highlights the necessity for extracellular protein folding factors governing MRSA β-lactam resistance. Targeting the PBP2a folding pathway represents a particularly attractive adjuvant strategy to combat antibiotic resistance.

scholarly journals Simulation of Two-Dimensional Ultraviolet Spectroscopy of Amyloid Fibrils

2010 ◽  
Vol 114 (37) ◽  
pp. 12150-12156 ◽  
Author(s):  
Jun Jiang ◽  
Darius Abramavicius ◽  
Cyril Falvo ◽  
Benjamin M. Bulheller ◽  
Jonathan D. Hirst ◽  
...  
Keyword(s):  
Amyloid Fibrils ◽  
Ultraviolet Spectroscopy ◽  
Two Dimensional

Abstract 4268: Protein folding pathway modulation upon Hsp70 inhibition in cancer cells

2019 ◽  
Author(s):  
Sara Sannino ◽  
Christopher J. Guerriero ◽  
Amit J. Sabnis ◽  
Jeffrey J. Bridsky
Keyword(s):  
Protein Folding ◽  
Cancer Cells ◽  
Folding Pathway

scholarly journals Different Routes of Protein Folding Contribute to Improved Protein Production in Saccharomyces cerevisiae

mBio ◽  
2020 ◽  
Vol 11 (6) ◽  
Author(s):  
Qi Qi ◽  
Feiran Li ◽  
Rosemary Yu ◽  
Martin K. M. Engqvist ◽  
Verena Siewers ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Protein Folding ◽  
Recombinant Protein ◽  
Recombinant Protein Production ◽  
Protein Production ◽  
Strain Engineering ◽  
Folding Pathway ◽  
Original Strain ◽  
Precision Control ◽  
Folding Process

ABSTRACT Protein folding is often considered the flux controlling process in protein synthesis and secretion. Here, two previously isolated Saccharomyces cerevisiae strains with increased α-amylase productivity were analyzed in chemostat cultures at different dilution rates using multi-omics data. Based on the analysis, we identified different routes of the protein folding pathway to improve protein production. In the first strain, the increased abundance of proteins working on the folding process, coordinated with upregulated glycogen metabolism and trehalose metabolism, helped increase α-amylase productivity 1.95-fold compared to the level in the original strain in chemostat culture at a dilution rate of 0.2/h. The second strain further strengthened the folding precision to improve protein production. More precise folding helps the cell improve protein production efficiency and reduce the expenditure of energy on the handling of misfolded proteins. As calculated using an enzyme-constrained genome-scale metabolic model, the second strain had an increased productivity of 2.36-fold with lower energy expenditure than that of the original under the same condition. Further study revealed that the regulation of N-glycans played an important role in the folding precision control and that overexpression of the glucosidase Cwh41p can significantly improve protein production, especially for the strains with improved folding capacity but lower folding precision. Our findings elucidated in detail the mechanisms in two strains having improved protein productivity and thereby provided novel insights for industrial recombinant protein production as well as demonstrating how multi-omics analysis can be used for identification of novel strain-engineering targets. IMPORTANCE Protein folding plays an important role in protein maturation and secretion. In recombinant protein production, many studies have focused on the folding pathway to improve productivity. Here, we identified two different routes for improving protein production by yeast. We found that improving folding precision is a better strategy. Dysfunction of this process is also associated with several aberrant protein-associated human diseases. Here, our findings about the role of glucosidase Cwh41p in the precision control system and the characterization of the strain with a more precise folding process could contribute to the development of novel therapeutic strategies.

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