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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)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
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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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Nf-kappa-b; Essential Modulator Nemo; Free-energy Landscapes; Bead Form-factors; Ubiquitin Chains; Protein; Recognition; Complex; Conformations; Contributes
Sprache englisch
Veröffentlichungsjahr 2020
HGF-Berichtsjahr 2020
ISSN (print) / ISBN 2375-2548
e-ISSN 2375-2548
Zeitschrift Science Advances
Quellenangaben Band: 6, Heft: 42, Seiten: , Artikelnummer: eabc3786 Supplement: ,
Verlag American Association for the Advancement of Science (AAAS)
Verlagsort Washington, DC [u.a.]
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Structural Biology (STB)
POF Topic(s) 30203 - Molecular Targets and Therapies
Forschungsfeld(er) Enabling and Novel Technologies
PSP-Element(e) G-503000-001
Förderungen Gauss Centre for Supercomputing e.V.
Lundbeck Foundation
DFG
European Union Seventh Framework Programme
Technische Universitat Munchen-Institute for Advanced Study - German Excellence Initiative
DOI 10.1126/sciadv.abc3786
WOS ID WOS:000579164600027
Scopus ID 85093481472
PubMed ID 33055165
Erfassungsdatum 2020-11-13
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