King's College London

Research portal

The cold denaturation of IscU highlights structure–function dualism in marginally stable proteins

Research output: Contribution to journalArticlepeer-review

Robert Yan, Paolo DeLos Rios, Annalisa Pastore, Piero Andrea Temussi

Original languageEnglish
Article number13
JournalCommunications Chemistry
Issue number1
Accepted/In press5 Feb 2018
Published1 Dec 2018

King's Authors

Research Groups

  • King's College London


Proteins undergo both cold and heat denaturation, but often cold denaturation cannot be detected because it occurs at temperatures below water freezing. Proteins undergoing detectable cold as well as heat denaturation yield a reliable curve of protein stability. Here we use bacterial IscU, an essential and ancient protein involved in iron cluster biogenesis, to show an important example of unbiased cold denaturation, based on electrostatic frustration caused by a dualism between iron–sulfur cluster binding and the presence of a functionally essential electrostatic gate. We explore the structural determinants and the universals that determine cold denaturation with the aid of a coarse grain model. Our results set a firm point in our understanding of cold denaturation and give us general rules to induce and predict protein cold denaturation. The conflict between ligand binding and stability hints at the importance of the structure–function dualism in protein evolution.

View graph of relations

© 2020 King's College London | Strand | London WC2R 2LS | England | United Kingdom | Tel +44 (0)20 7836 5454