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Jussupow, A.* ; Messias, A.C. ; Stehle, R. ; Geerlof, A. ; Solbak, S.M.Ø.* ; Paissoni, C.* ; Bach, A.* ; Sattler, M. ; Camilloni, C.*

The dynamics of linear polyubiquitin.

Sci. Adv. 6:eabc3786 (2020)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Polyubiquitin chains are flexible multidomain proteins, whose conformational dynamics enable them to regulate multiple biological pathways. Their dynamic is determined by the linkage between ubiquitins and by the number of ubiquitin units. Characterizing polyubiquitin behavior as a function of their length is hampered because of increasing system size and conformational variability. Here, we introduce a new approach to efficiently integrating small- angle x-ray scattering with simulations allowing us to accurately characterize the dynamics of linear di-, tri-, and tetraubiquitin in the free state as well as of diubiquitin in complex with NEMO, a central regulator in the NF-kappa B pathway. Our results show that the behavior of the diubiquitin subunits is independent of the presence of additional ubiquitin modules and that the dynamics of polyubiquitins with different lengths follow a simple model. Together with experimental data from multiple biophysical techniques, we then rationalize the 2:1 NEMO:polyubiquitin binding.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Nf-kappa-b; Essential Modulator Nemo; Free-energy Landscapes; Bead Form-factors; Ubiquitin Chains; Protein; Recognition; Complex; Conformations; Contributes
ISSN (print) / ISBN 2375-2548
e-ISSN 2375-2548
Quellenangaben Volume: 6, Issue: 42, Pages: , Article Number: eabc3786 Supplement: ,
Publisher American Association for the Advancement of Science (AAAS)
Publishing Place Washington, DC [u.a.]
Non-patent literature Publications
Reviewing status Peer reviewed
Grants Gauss Centre for Supercomputing e.V.
Lundbeck Foundation
DFG
European Union Seventh Framework Programme
Technische Universitat Munchen-Institute for Advanced Study - German Excellence Initiative