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Cell-wide analysis of protein thermal unfolding reveals determinants of thermostability


Leuenberger, Pascal; Ganscha, Stefan; Kahraman, Abdullah; Cappelletti, Valentina; Boersema, Paul J; von Mering, Christian; Claassen, Manfred; Picotti, Paola (2017). Cell-wide analysis of protein thermal unfolding reveals determinants of thermostability. Science, 355(6327):1-13.

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 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.

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 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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Institute of Molecular Life Sciences
08 University Research Priority Programs > Systems Biology / Functional Genomics
08 University Research Priority Programs > Evolution in Action: From Genomes to Ecosystems
Dewey Decimal Classification:570 Life sciences; biology
Language:English
Date:24 February 2017
Deposited On:06 Oct 2017 06:39
Last Modified:09 Dec 2017 02:34
Publisher:American Association for the Advancement of Science
ISSN:0036-8075
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1126/science.aai7825
PubMed ID:28232526

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