HUWE1 employs a giant substrate-binding ring to feed and
regulate its HECT E3 domain

J 2021

HUWE1 employs a giant substrate-binding ring to feed and regulate its HECT E3 domain

GRABARCZYK, D.B., O.A. PETROVA, L. DESZCZ, R. KURZBAUER, P. MURPHY et. al.

Základní údaje

Originální název

HUWE1 employs a giant substrate-binding ring to feed and regulate its HECT E3 domain

Autoři

Vydání

Nature Chemical Biology, BERLIN, NATURE PORTFOLIO, 2021, 1552-4450

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10608 Biochemistry and molecular biology

Stát vydavatele

Německo

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 16.174

Kód RIV

RIV/00216224:14740/21:00124444

Organizační jednotka

Středoevropský technologický institut

DOI

http://dx.doi.org/10.1038/s41589-021-00831-5

UT WoS

000675784100001

Klíčová slova anglicky

Animals; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Fungal Proteins; Insecta; Microsporidia

Štítky

CF CRYO, ne MU, rivok

Změněno: 23. 3. 2022 12:23, Mgr. Pavla Foltynová, Ph.D.

Anotace

V originále

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.

Návaznosti

90127, velká výzkumná infrastruktura

Název: CIISB II

Citovat

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 a T. CLAUSEN. HUWE1 employs a giant substrate-binding ring to feed and regulate its HECT E3 domain. Nature Chemical Biology. BERLIN: NATURE PORTFOLIO, 2021, roč. 17, č. 10, s. 1084-1092. ISSN 1552-4450. Dostupné z: https://dx.doi.org/10.1038/s41589-021-00831-5.

@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 a 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, roč.~17, č.~10, s.~1084-1092. ISSN~1552-4450. Dostupné z: https://dx.doi.org/10.1038/s41589-021-00831-5.

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