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Updated: Jul 19, 2025

Investigating Protein Sequence-structure-dynamics Relationships with Bio3D-web
Published on: July 16, 2017
Specifying conformational heterogeneity of multi-domain proteins at atomic resolution
Tobias Schneider1, Kevin Sawade2, Frederic Berner1
1Department of Chemistry, University of Konstanz, 78457 Konstanz, Germany; Konstanz Research School Chemical Biology, University of Konstanz, 78457 Konstanz, Germany.
Abstract:
The conformational landscape of multi-domain proteins is inherently linked to their specific functions. This also holds for polyubiquitin chains that are assembled by two or more ubiquitin domains connected by a flexible linker thus showing a large interdomain mobility. However, molecular recognition and signal transduction are associated with particular conformational substates that are populated in solution. Here, we apply high-resolution NMR spectroscopy in combination with dual-scale MD simulations to explore the conformational space of K6-, K29-, and K33-linked diubiquitin molecules. The conformational ensembles are evaluated utilizing a paramagnetic cosolute reporting on solvent exposure plus a set of complementary NMR parameters. This approach unravels a conformational heterogeneity of diubiquitins and explains the diversity of structural models that have been determined for K6-, K29-, and K33-linked diubiquitins in free and ligand-bound states so far. We propose a general application of the approach developed here to demystify multi-domain proteins occurring in nature.
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