title: Global analysis of protein structural changes in complex proteomes.
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.
authors.affiliation: 1] Institute of Biochemistry, Department of Biology, ETH Zurich, Zurich, Switzerland. [2].
authors.forename: Yuehan
authors.initials: Y
authors.lastname: Feng
authors.affiliation: 1] Institute of Biochemistry, Department of Biology, ETH Zurich, Zurich, Switzerland. [2] CRIBI Biotechnology Centre, University of Padua, Padua, Italy. [3].
authors.forename: Giorgia
authors.initials: G
authors.lastname: De Franceschi
authors.affiliation: 1] Institute of Biochemistry, Department of Biology, ETH Zurich, Zurich, Switzerland. [2].
authors.forename: Abdullah
authors.identifier: 0000000335234467
authors.initials: A
authors.lastname: Kahraman
authors.affiliation: Institute of Biochemistry, Department of Biology, ETH Zurich, Zurich, Switzerland.
authors.forename: Martin
authors.initials: M
authors.lastname: Soste
authors.affiliation: Institute of Biochemistry, Department of Biology, ETH Zurich, Zurich, Switzerland.
authors.forename: Andre
authors.initials: A
authors.lastname: Melnik
authors.affiliation: Institute of Biochemistry, Department of Biology, ETH Zurich, Zurich, Switzerland.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Boersema
authors.affiliation: CRIBI Biotechnology Centre, University of Padua, Padua, Italy.
authors.forename: Patrizia Polverino
authors.initials: PP
authors.lastname: de Laureto
authors.affiliation: Institute of Molecular Biology and Biophysics, Department of Biology, ETH Zurich, Zurich, Switzerland.
authors.forename: Yaroslav
authors.initials: Y
authors.lastname: Nikolaev
authors.affiliation: Institute of Molecular Systems Biology, Department of Biology, ETH Zurich, Zurich, Switzerland.
authors.forename: Ana Paula
authors.identifier: 0000000337879138
authors.initials: AP
authors.lastname: Oliveira
authors.affiliation: Institute of Biochemistry, Department of Biology, ETH Zurich, Zurich, Switzerland.
authors.forename: Paola
authors.initials: P
authors.lastname: Picotti
mesh_terms: D000595:Amino Acid Sequence; D000682:Amyloid; D005635:Fructosediphosphates; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D010446:Peptide Fragments; D011328:Prions; D011487:Protein Conformation; D011506:Proteins / Q000032:analysis* / Q000737:chemistry*; D059748:Proteolysis; D020543:Proteome / Q000032:analysis* / Q000737:chemistry*; D040901:Proteomics / Q000379:methods*; D014357:Trypsin
chemical_list: D000682:Amyloid; D005635:Fructosediphosphates; D010446:Peptide Fragments; D011328:Prions; D011506:Proteins; D020543:Proteome; D014357:Trypsin; C029063:fructose-1,6-diphosphate