| GRABARCZYK, D.B., O.A. PETROVA, L. DESZCZ, R. KURZBAUER, P. MURPHY, J. AHEL, A. VOGEL, R. GOGOVA, V. FAAS, D. KORDIC, A. SCHLEIFFER, A. MEINHART, R. IMRE, A. LEHNER, J. NEUHOLD, G. BADER, P. STOLT-BERGNER, J. BOTTCHER, B. WOLKERSTORFER, G. FISCHER, I. GRISHKOVSKAYA, D. HASELBACH, D. KESSLER and T. CLAUSEN. HUWE1 employs a giant substrate-binding ring to feed and regulate its HECT E3 domain. Nature Chemical Biology. BERLIN: NATURE PORTFOLIO, 2021, vol. 17, No 10, p. 1084-1092. ISSN 1552-4450. Available from: https://dx.doi.org/10.1038/s41589-021-00831-5. |
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@article{1842615,
author = {Grabarczyk, D.B. and Petrova, O.A. and Deszcz, L. and Kurzbauer, R. and Murphy, P. and Ahel, J. and Vogel, A. and Gogova, R. and Faas, V. and Kordic, D. and Schleiffer, A. and Meinhart, A. and Imre, R. and Lehner, A. and Neuhold, J. and Bader, G. and StoltandBergner, P. and Bottcher, J. and Wolkerstorfer, B. and Fischer, G. and Grishkovskaya, I. and Haselbach, D. and Kessler, D. and Clausen, T.},
article_location = {BERLIN},
article_number = {10},
doi = {http://dx.doi.org/10.1038/s41589-021-00831-5},
keywords = {Animals; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Fungal Proteins; Insecta; Microsporidia},
language = {eng},
issn = {1552-4450},
journal = {Nature Chemical Biology},
title = {HUWE1 employs a giant substrate-binding ring to feed and regulate its HECT E3 domain},
url = {https://www.nature.com/articles/s41589-021-00831-5},
volume = {17},
year = {2021}
}
TY - JOUR
ID - 1842615
AU - Grabarczyk, D.B. - Petrova, O.A. - Deszcz, L. - Kurzbauer, R. - Murphy, P. - Ahel, J. - Vogel, A. - Gogova, R. - Faas, V. - Kordic, D. - Schleiffer, A. - Meinhart, A. - Imre, R. - Lehner, A. - Neuhold, J. - Bader, G. - Stolt-Bergner, P. - Bottcher, J. - Wolkerstorfer, B. - Fischer, G. - Grishkovskaya, I. - Haselbach, D. - Kessler, D. - Clausen, T.
PY - 2021
TI - HUWE1 employs a giant substrate-binding ring to feed and regulate its HECT E3 domain
JF - Nature Chemical Biology
VL - 17
IS - 10
SP - 1084-1092
EP - 1084-1092
PB - NATURE PORTFOLIO
SN - 15524450
KW - Animals
KW - Caenorhabditis elegans
KW - Caenorhabditis elegans Proteins
KW - Fungal Proteins
KW - Insecta
KW - Microsporidia
UR - https://www.nature.com/articles/s41589-021-00831-5
N2 - HUWE1 is a universal quality-control E3 ligase that marks diverse client proteins for proteasomal degradation. Although the giant HECT enzyme is an essential component of the ubiquitin-proteasome system closely linked with severe human diseases, its molecular mechanism is little understood. Here, we present the crystal structure of Nematocida HUWE1, revealing how a single E3 enzyme has specificity for a multitude of unrelated substrates. The protein adopts a remarkable snake-like structure, where the C-terminal HECT domain heads an extended alpha-solenoid body that coils in on itself and houses various protein-protein interaction modules. Our integrative structural analysis shows that this ring structure is highly dynamic, enabling the flexible HECT domain to reach protein targets presented by the various acceptor sites. Together, our data demonstrate how HUWE1 is regulated by its unique structure, adapting a promiscuous E3 ligase to selectively target unassembled orphan proteins.
ER -
GRABARCZYK, D.B., O.A. PETROVA, L. DESZCZ, R. KURZBAUER, P. MURPHY, J. AHEL, A. VOGEL, R. GOGOVA, V. FAAS, D. KORDIC, A. SCHLEIFFER, A. MEINHART, R. IMRE, A. LEHNER, J. NEUHOLD, G. BADER, P. STOLT-BERGNER, J. BOTTCHER, B. WOLKERSTORFER, G. FISCHER, I. GRISHKOVSKAYA, D. HASELBACH, D. KESSLER and T. CLAUSEN. HUWE1 employs a giant substrate-binding ring to feed and regulate its HECT E3 domain. \textit{Nature Chemical Biology}. BERLIN: NATURE PORTFOLIO, 2021, vol.~17, No~10, p.~1084-1092. ISSN~1552-4450. Available from: https://dx.doi.org/10.1038/s41589-021-00831-5.
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