Characterisation of HOIP RBR E3 ligase conformational dynamics using integrative modelling

Marius Kausas, Diego Esposito, Katrin Rittinger, Franca Fraternali

Research output: Contribution to journalArticlepeer-review


Multidomain proteins composed of individual domains connected by flexible linkers pose a challenge for structural studies due to their intrinsic conformational dynamics. Integrated modelling approaches provide a means to characterise protein flexibility by combining experimental measurements with molecular simulations. In this study, we characterise the conformational dynamics of the catalytic RBR domain of the E3 ubiquitin ligase HOIP, which regulates immune and inflammatory signalling pathways. Specifically, we combine small angle X-ray scattering experiments and molecular dynamics simulations to generate weighted conformational ensembles of the HOIP RBR domain using two different approaches based on maximum parsimony and maximum entropy principles. Both methods provide optimised ensembles that are instrumental in rationalising observed differences between SAXS-based solution studies and available crystal structures and highlight the importance of interdomain linker flexibility.

Original languageEnglish
Article number15201
Pages (from-to)15201
Number of pages1
JournalScientific Reports
Issue number1
Publication statusPublished - 8 Sept 2022


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