Periplasmic Protein HdeA Exhibits Chaperone-like Activity Exclusively within Stomach pH Range by Transforming into Disordered Conformation
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The extremely acidic environment of the mammalian stomach, with a pH range usually between 1 and 3, represents a stressful challenge for enteric pathogenic bacteria such as Escherichia coli before they enter into the intestine. The hdeA gene of E. coli was found to be acid inducible and was revealed by genetic studies to be important for the acid survival of the strain. This study was performed in an attempt to characterize the mechanism of the activity of the HdeA protein. Our data provided in this report strongly suggest that HdeA employs a novel strategy to modulate its chaperone activity: it possesses an ordered conformation that is unable to bind denatured substrate proteins under normal physiological conditions (i.e. at neutral pH) and transforms into a globally disordered conformation that is able to bind substrate proteins under stress conditions (i.e. at a pH below 3). Furthermore, our data indicate that HdeA exposes hydrophobic surfaces that appear to be involved in the binding of denatured substrate proteins at extremely low pH values. In light of our observations, models are proposed to explain the action of HdeA in both a physiological and a molecular context.
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The E. coli periplasmic protein HdeA behaves as an acid-inducible chaperone.
“Likewise, the E. coli periplasmic protein HdeA behaves as an acid-inducible chaperone [227].”
From Intrinsically disordered proteins play diverse roles in cell signaling (2022) · cites this paper as [227]
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- Papoian, G. A., Ulander, J., Eastwood, M. P., Luthey-Schulten, Z., and Wolynes, P. G. (2004) Proc. Natl. Acad. Sci. U. S. A. 101, 3352-3357
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Intrinsically disordered proteins play diverse roles in cell signaling
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- Authors
- Hong, W., Jiao, W., Hu, J., Zhang, J., Liu, C., Fu, X., Shen, D., Xia, B., & Chang, Z.
- Affiliations
- Peking University (CN)
- Tsinghua University (CN)
- Corresponding author
- Chang, Zengyi
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2005-07
- Volume
- 280
- Issue
- 29
- Pages
- 27029-27034
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2010924361
- Cited by
- 132
- References
- 27
- Citations by year
- 2026: 4 · 2025: 1 · 2024: 2 · 2023: 2 · 2022: 4 · 2021: 4 · 2020: 6 · 2019: 9 · 2018: 8 · 2017: 8 · 2016: 10 · 2015: 10 · 2014: 8 · 2013: 8 · 2012: 15
- FWCI
- 1.87
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Science Foundation
- National Natural Science Foundation of China (30270289, 30125009)
- Chinese Academy of Sciences
- Tsinghua University
- Institute of Biophysics, Chinese Academy of Sciences
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Keywords
- HdeA, periplasmic chaperone, intrinsically disordered proteins, Escherichia coli, acid stress, gastric pH, protein refolding, hydrophobic surface exposure, chaperone activity
- MeSH terms
- Gene Expression Regulation, Hydrogen-Ion Concentration, Protein Binding, Protein Conformation, Protein Denaturation, Stomach, Molecular Chaperones, Escherichia coli Proteins, Periplasmic Proteins, Hydrophobic and Hydrophilic Interactions
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