title: Cell-wide analysis of protein thermal unfolding reveals determinants of thermostability.
abstract: Temperature-induced cell death is thought to be due to protein denaturation, but the determinants of thermal sensitivity of proteomes remain largely uncharacterized. We developed a structural proteomic strategy to measure protein thermostability on a proteome-wide scale and with domain-level resolution. We applied it toEscherichia coli,Saccharomyces cerevisiae,Thermus thermophilus, and human cells, yielding thermostability data for more than 8000 proteins. Our results (i) indicate that temperature-induced cellular collapse is due to the loss of a subset of proteins with key functions, (ii) shed light on the evolutionary conservation of protein and domain stability, and (iii) suggest that natively disordered proteins in a cell are less prevalent than predicted and (iv) that highly expressed proteins are stable because they are designed to tolerate translational errors that would lead to the accumulation of toxic misfolded species.
authors.affiliation: Institute of Biochemistry, Department of Biology, ETH Zurich (ETHZ), CH-8093 Zurich, Switzerland.|Systems Biology Graduate School PhD Program, ETHZ and University of Zurich, CH-8093 Zurich, Switzerland.
authors.forename: Pascal
authors.identifier: 0000-0002-7597-3531
authors.initials: P
authors.lastname: Leuenberger
authors.affiliation: Systems Biology Graduate School PhD Program, ETHZ and University of Zurich, CH-8093 Zurich, Switzerland.|Institute of Molecular Systems Biology, Department of Biology, ETHZ, CH-8093 Zurich, Switzerland.
authors.forename: Stefan
authors.initials: S
authors.lastname: Ganscha
authors.affiliation: Institute of Molecular Life Sciences and Swiss Institute of Bioinformatics, University of Zurich, CH-8057 Zurich, Switzerland.
authors.forename: Abdullah
authors.identifier: 0000-0003-3523-4467
authors.initials: A
authors.lastname: Kahraman
authors.affiliation: Institute of Biochemistry, Department of Biology, ETH Zurich (ETHZ), CH-8093 Zurich, Switzerland.
authors.forename: Valentina
authors.initials: V
authors.lastname: Cappelletti
authors.affiliation: Institute of Biochemistry, Department of Biology, ETH Zurich (ETHZ), CH-8093 Zurich, Switzerland.
authors.forename: Paul J
authors.identifier: 0000-0002-0646-0070
authors.initials: PJ
authors.lastname: Boersema
authors.affiliation: Institute of Molecular Life Sciences and Swiss Institute of Bioinformatics, University of Zurich, CH-8057 Zurich, Switzerland.
authors.forename: Christian
authors.identifier: 0000-0001-7734-9102
authors.initials: C
authors.lastname: von Mering
authors.affiliation: Institute of Molecular Systems Biology, Department of Biology, ETHZ, CH-8093 Zurich, Switzerland.
authors.forename: Manfred
authors.initials: M
authors.lastname: Claassen
authors.affiliation: Institute of Biochemistry, Department of Biology, ETH Zurich (ETHZ), CH-8093 Zurich, Switzerland. paola.picotti@bc.biol.ethz.ch.
authors.forename: Paola
authors.identifier: 0000-0003-1012-9994
authors.initials: P
authors.lastname: Picotti
mesh_terms: D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D006801:Humans; D013058:Mass Spectrometry; D011489:Protein Denaturation; D060066:Protein Interaction Maps; D055550:Protein Stability; D058767:Protein Unfolding; D011506:Proteins / Q000737:chemistry*; D059748:Proteolysis; D020543:Proteome / Q000737:chemistry; D040901:Proteomics / Q000379:methods; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D013696:Temperature; D016963:Thermus thermophilus / Q000235:genetics / Q000378:metabolism
chemical_list: D011506:Proteins; D020543:Proteome