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Nat Biotechnol. 2014 Oct;32(10):1036-44. doi: 10.1038/nbt.2999. Epub 2014 Sep 14.

Global analysis of protein structural changes in complex proteomes.

Author information

1
1] Institute of Biochemistry, Department of Biology, ETH Zurich, Zurich, Switzerland. [2].
2
1] Institute of Biochemistry, Department of Biology, ETH Zurich, Zurich, Switzerland. [2] CRIBI Biotechnology Centre, University of Padua, Padua, Italy. [3].
3
Institute of Biochemistry, Department of Biology, ETH Zurich, Zurich, Switzerland.
4
CRIBI Biotechnology Centre, University of Padua, Padua, Italy.
5
Institute of Molecular Biology and Biophysics, Department of Biology, ETH Zurich, Zurich, Switzerland.
6
Institute of Molecular Systems Biology, Department of Biology, ETH Zurich, Zurich, Switzerland.

Abstract

Changes in protein conformation can affect protein function, but methods to probe these structural changes on a global scale in cells have been lacking. To enable large-scale analyses of protein conformational changes directly in their biological matrices, we present a method that couples limited proteolysis with a targeted proteomics workflow. Using our method, we assessed the structural features of more than 1,000 yeast proteins simultaneously and detected altered conformations for ~300 proteins upon a change of nutrients. We find that some branches of carbon metabolism are transcriptionally regulated whereas others are regulated by enzyme conformational changes. We detect structural changes in aggregation-prone proteins and show the functional relevance of one of these proteins to the metabolic switch. This approach enables probing of both subtle and pronounced structural changes of proteins on a large scale.

PMID:
25218519
DOI:
10.1038/nbt.2999
[Indexed for MEDLINE]

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