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NMR Biomed. 2015 Jul;28(7):906-13. doi: 10.1002/nbm.3317. Epub 2015 May 26.

Signature of protein unfolding in chemical exchange saturation transfer imaging.

Author information

1
Division of Medical Physics in Radiology, Deutsches Krebsforschungszentrum [German Cancer Research Center] (DKFZ), Heidelberg, Baden-Württemberg, Germany.
2
Division of Functional Genome Analysis, Deutsches Krebsforschungszentrum [German Cancer Research Center] (DKFZ), Heidelberg, Baden-Württemberg, Germany.
3
Molecular Structure Analysis, Deutsches Krebsforschungszentrum [German Cancer Research Center] (DKFZ), Heidelberg, Baden-Württemberg, Germany.
4
Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH), DKFZ-ZMBH Allianz, Heidelberg, Baden-Württemberg, Germany.
5
Deutsches Krebsforschungszentrum [German Cancer Research Center] (DKFZ), Heidelberg, Baden-Württemberg, Germany.

Abstract

Chemical exchange saturation transfer (CEST) allows the detection of metabolites of low concentration in tissue with nearly the sensitivity of MRI with water protons. With this spectroscopic imaging approach, several tissue-specific CEST effects have been observed in vivo. Some of these originate from exchanging sites of proteins, such as backbone amide protons, or from aliphatic protons within the hydrophobic protein core. In this work, we employed CEST experiments to detect global protein unfolding. Spectral evaluation revealed exchange- and NOE-mediated CEST effects that varied in a highly characteristic manner with protein unfolding tracked by fluorescence spectroscopy. We suggest the use of this comprehensive spectral signature for the detection of protein unfolding by CEST, as it relies on several spectral hallmarks. As proof of principle, we demonstrate that the presented signature is readily detectable using a whole-body MR tomograph (B0  = 7 T), not only in denatured aqueous protein solutions, but also in heat-shocked yeast cells. A CEST imaging contrast with the potential to detect global protein unfolding would be of particular interest regarding protein unfolding as a marker for stress, ageing, and disease.

KEYWORDS:

BSA; CEST; NOE; chemical exchange; protein unfolding; yeast

PMID:
26010522
DOI:
10.1002/nbm.3317
[Indexed for MEDLINE]

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