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
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• PubMed

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Journal Article | Research Support, Non-U.S. Gov't

Authors

Feng Y, De Franceschi G, Kahraman A, Soste M, Melnik A, Boersema PJ, de Laureto PP, Nikolaev Y, Oliveira AP, Picotti P

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