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Conformational order in an intrinsically disordered protein 

Post-translational modification of proteins with ubiquitin represents a widely used mechanism for cellular regulation. Ubiquitin is covalently linked to the targeted protein by an E3 ligase. Although the human genome contains an estimated 600 E3 ligases, there is limited information about how they function. A collaboration between Steve Matthews (Centre for Structural Biology, Imperial College London), Ron Hay (Centre of Gene Regulation and Expression, University  of Dundee) and Carlos Penedo (Centre of Biophotonics, University of St Andrews) provides insights into this mechanism. Using NMR paramagnetic relaxation enhancement (PRE), smFRET and molecular dynamic simulations they quantified the flexibility of the E3 ligase unstructured domain. This work demonstrates, for the first time, how charge segmentation allows intrinsically disordered proteins to adopt preferred structures that are essential for function.

The paper was first published on 31 July 2020 in Nature Communications and can be accessed by its DOI: https://doi.org/10.1038/s41467-020-17647-x