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Eur Biophys J. 2018 Jan;47(1):89-94. doi: 10.1007/s00249-017-1260-4. Epub 2017 Oct 27.

Denaturant-specific effects on the structural energetics of a protein-denatured ensemble.

Author information

1
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA.
2
Department of Pharmacology & Chemical Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA.
3
Department of Chemistry, Chonnam National University, Gwangju, 500-757, Republic of Korea.
4
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA. allan.ferreon@bcm.edu.
5
Department of Pharmacology & Chemical Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA. allan.ferreon@bcm.edu.
6
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA. deniz@scripps.edu.

Abstract

Protein thermodynamic stability is intricately linked to cellular function, and altered stability can lead to dysfunction and disease. The linear extrapolation model (LEM) is commonly used to obtain protein unfolding free energies ([Formula: see text]) by extrapolation of solvent denaturation data to zero denaturant concentration. However, for some proteins, different denaturants result in non-coincident LEM-derived [Formula: see text] values, raising questions about the inherent assumption that the obtained [Formula: see text] values are intrinsic to the protein. Here, we used single-molecule FRET measurements to better understand such discrepancies by directly probing changes in the dimensions of the protein G B1 domain (GB1), a well-studied protein folding model, upon urea and guanidine hydrochloride denaturation. A comparison of the results for the two denaturants suggests denaturant-specific structural energetics in the GB1 denatured ensemble, revealing a role of the denatured state in the variable thermodynamic behavior of proteins.

KEYWORDS:

Protein folding; Single-molecule FRET; Solvent unfolding; Two-state folding; Variable thermodynamics

PMID:
29080139
DOI:
10.1007/s00249-017-1260-4
[Indexed for MEDLINE]

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