The dynamics of linear polyubiquitin
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The dynamics of linear polyubiquitin. / Jussupow, Alexander; Messias, Ana C.; Stehle, Ralf; Geerlof, Arie; Solbak, Sara Marie Øie; Paissoni, Cristina; Bach, Anders; Sattler, Michael; Camilloni, Carlo.
In: Science Advances, Vol. 6, No. 42, eabc3786, 10.2020.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - The dynamics of linear polyubiquitin
AU - Jussupow, Alexander
AU - Messias, Ana C.
AU - Stehle, Ralf
AU - Geerlof, Arie
AU - Solbak, Sara Marie Øie
AU - Paissoni, Cristina
AU - Bach, Anders
AU - Sattler, Michael
AU - Camilloni, Carlo
PY - 2020/10
Y1 - 2020/10
N2 - 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-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.
AB - 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-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.
U2 - 10.1126/sciadv.abc3786
DO - 10.1126/sciadv.abc3786
M3 - Journal article
C2 - 33055165
AN - SCOPUS:85093481472
VL - 6
JO - Science advances
JF - Science advances
SN - 2375-2548
IS - 42
M1 - eabc3786
ER -
ID: 251360449