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Oxidative Folding: Coupling Conformational Folding and Disulfide Formation

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Folding of Disulfide Proteins

Part of the book series: Protein Reviews ((PRON,volume 14))

Abstract

Determining how a string of amino acid residues folds into the ­biologically active protein conformation remains as one of the most important and challenging tasks in biology. Protein folding is usually a fast reaction in which transient intermediates in the folding pathway are short lived, highly dynamic, and very difficult to be trapped, isolated, and characterized. The technique of oxidative folding applied to study disulfide proteins overcomes some of these problems. During protein oxidative folding, the coupling between conformational folding and disulfide formation together with the possibility to selectively quench the progress of the oxidative reaction permits the isolation and further structural characterization of transient folding intermediates in atomic detail. With its unique chemistry and relatively slow kinetics of disulfide formation, the technique of oxidative folding has facilitated the detailed characterization of the folding pathways of an important number of disulfide-rich proteins. The results reveal a high degree of diversity of folding mechanisms, which are mainly manifested by the extent of heterogeneity and native-like structures of their intermediate ensembles. Overall, as we will discuss in this chapter, the study of disulfide-containing polypeptides has contributed significantly to our current knowledge on the molecular basis of protein folding.

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Abbreviations

(des) species:

A folding intermediate lacking one disulfide bond

1S:

One-disulfide intermediates

2S:

Two-disulfide intermediates

3D structure:

Three-dimensional structure

3S:

Three-disulfide intermediates

BPTI:

Bovine pancreatic trypsin inhibitor

Cys–Cys:

Cystine

DTTox:

Oxidized dithiothreitol

DTTred :

Reduced dithiothreitol

EGF:

Epidermal growth factor

GSH:

Reduced glutathione

GSSG:

Oxidized glutathione

H/D exchange:

Hydrogen to deuterium exchange

LCI:

Leech carboxypeptidase inhibitor

LDTI:

Leech-derived trypsin inhibitor

MCoTI-II:

Momordica cochinchinensis trypsin inhibitor II

MS:

Mass spectrometry

PDI:

Protein disulfide isomerase

RNase A:

Bovine pancreatic ribonuclease A

RP-HPLC:

Reversed phase high-performance liquid chromatography

S-:

Thiolate group

SH:

Thiol group

TAP:

Tick anticoagulant peptide

TCEP:

Tris(2-carboxyethyl)phosphine

TCI:

Tick carboxypeptidase inhibitor

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Authors and Affiliations

  1. Institut de Biotecnologia i de Biomedicina and Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra, 08193, Barcelona, Spain

    Salvador Ventura

  2. Research Center for Protein Chemistry, Brown Foundation Institute of Molecular Medicine, 1825 Pressler Street, Houston, TX, 77030, USA

    Rowen J. Y. Chang

  3. Department of Biochemistry and Molecular Biology, The University of Texas, Houston, TX, 77030, USA

    Rowen J. Y. Chang

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  1. Salvador Ventura
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Correspondence to Salvador Ventura .

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Editors and Affiliations

  1. Brown Foundation Inst. of Molecular Medi, The University of Texas, Houston, 77030, Texas, USA

    Rowen J. Y. Chang

  2. Institut de Biotecnologia i de Biomed., Dept. de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra, 08193, Spain

    Salvador Ventura

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Ventura, S., Chang, R.J.Y. (2011). Oxidative Folding: Coupling Conformational Folding and Disulfide Formation. In: Chang, R., Ventura, S. (eds) Folding of Disulfide Proteins. Protein Reviews, vol 14. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-7273-6_1

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