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Updated: Jun 19, 2026

In Vitro Analysis of E3 Ubiquitin Ligase Function
Published on: May 14, 2021
Conformational selection and induced fit mechanism underlie specificity in noncovalent interactions with ubiquitin
Tomasz Wlodarski1, Bojan Zagrovic
1Laboratory of Bioinformatics and Bioengineering, Interdisciplinary Centre for Mathematical and Computational Modeling, University of Warsaw, Zwirki i Wigury 93 02-089, Warsaw, Poland.
Abstract:
Noncovalent binding interactions between proteins are the central physicochemical phenomenon underlying biological signaling and functional control on the molecular level. Here, we perform an extensive structural analysis of a large set of bound and unbound ubiquitin conformers and study the level of residual induced fit after conformational selection in the binding process. We show that the region surrounding the binding site in ubiquitin undergoes conformational changes that are significantly more pronounced compared with the whole molecule on average. We demonstrate that these induced-fit structural adjustments are comparable in magnitude to conformational selection. Our final model of ubiquitin binding blends conformational selection with the subsequent induced fit and provides a quantitative measure of their respective contributions.
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