on 03-03-201701:05 PM - edited on 10-15-202107:07 AM by Closed Account
Pascal Leuenberger,1,2 Stefan Ganscha,2,3 Abdullah Kahraman,4 Valentina Cappelletti,1 Paul J. Boersema,1 Christian von Mering,4 Manfred Claassen,3 Paola Picotti1
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 to Escherichia 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.
http://science.sciencemag.org/content/355/6327/eaai7825 1. Institute of Biochemistry, Department of Biology, ETH Zurich (ETHZ), CH-8093 Zurich, Switzerland.
2. Systems Biology Graduate School PhD Program, ETHZ and University of Zurich, CH-8093 Zurich, Switzerland.
3. Institute of Molecular Systems Biology, Department of Biology, ETHZ, CH-8093
4. Institute of Molecular Life Sciences and Swiss Institute of Bioinformatics, University of Zurich, CH-8057 Zurich, Switzerland.