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The Structure-Forming Juncture in Oxidative Protein Folding: What Happens in the ER?

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Protein Reviews

Part of the book series: Advances in Experimental Medicine and Biology ((PROTRE,volume 966))

Abstract

The folding of disulfide bond containing proteins proceeds in a biphasic manner. Initially, cysteines are oxidized to form disulfide bonds. Structure is largely absent during this phase. Next, when a minimally correct number of native linkages of disulfide bonds have been acquired, the biopolymer conformationally folds into the native, or a native-like, state. Thus, at the end of this “oxidative folding” process, a stable and biologically active protein is formed. This review focuses on dissecting the “structure-forming step” in oxidative protein folding. The ability to follow this pivotal step in protein maturation in somewhat detail is uniquely facilitated in “oxidative” folding scenarios. We review this step using bovine pancreatic Ribonuclease A as a model while recognizing the impact that this step has in subcellular trafficking and protein aggregation.

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Abbreviations

3SNNU :

Unstructured three-disulfide-bond-containing intermediate with one or more non-native disulfide linkages

3SNU :

Unstructured three-disulfide-bond-containing intermediate with native disulfide linkages

3SNUx,y,z :

Unstructured three-disulfide-bond-containing intermediate with native disulfide linkages where x, y and z, refer to the cis- or trans- orientations of the X-Pro peptide bonds around prolines 93, 114 and 117, respectively

Ux,y,z :

Unstructured disulfide-intact intermediate where x,y, and z refer to the cis- or trans- orientations of the X-Pro peptide bonds around prolines 93, 114 and 117, respectively

Des species:

a folding intermediate lacking one disulfide bond

DTTox :

Oxididized dithiothreitol

DTTred :

Reduced Dithiothreitol

ER:

Endoplamic Reticulum

GSH:

Reduced glutathione

GSSG:

Oxidized glutathione

RNase A:

bovine pancreatic ribonuclease A

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Acknowledgement

MN acknowledges NIH 1SC3 GM111200 01A1. The author wishes to thank Ms. Brenda Rubi Torres for creating some of the artwork in this chapter and Mr. Gyan M. Narayan for help with the manuscript. This work, is in part, an outcome of pedagogical techniques used by the author for a Biophysical Chemistry class taught by him in Spring 2016 (CHEM 4335). MN would like to acknowledge Jose A. Barragan, Homero R. Garcia, Natalia Luna, Vanessa I. Navarro, Stefani Perez Torres, and Alejandro Rodriguez for engaging in scintillating discussions on the subject of “The Structure-Forming Juncture in Oxidative Protein Folding: What happens in the ER?”

This work is in Compliance with Ethical Standards.

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The author declares no conflicts of interest.

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This article does not contain any studies with human participants or animals performed by any of the authors.

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Authors and Affiliations

  1. Department of Chemistry, The University of Texas at El Paso, 500 W. University Ave, El Paso, TX, USA, 79968

    Mahesh Narayan

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  1. Mahesh Narayan
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Correspondence to Mahesh Narayan .

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Editors and Affiliations

  1. Biochem and Mol Biol, Baylor College of Medicine, Houston, Texas, USA

    M. Zouhair Atassi

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Narayan, M. (2017). The Structure-Forming Juncture in Oxidative Protein Folding: What Happens in the ER?. In: Atassi, M. (eds) Protein Reviews. Advances in Experimental Medicine and Biology(), vol 966. Springer, Singapore. https://doi.org/10.1007/5584_2017_88

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