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A heterotypic assembly mechanism regulates CHIP E3 ligase activity
CHIP (C‐terminus of Hsc70‐interacting protein) and its worm ortholog CHN‐1 are E3 ubiquitin ligases that link the chaperone system with the ubiquitin‐proteasome system (UPS). CHN‐1 can cooperate with UFD‐2, another E3 ligase, to accelerate ubiquitin chain formation; however, the basis for the high p...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9340540/ https://www.ncbi.nlm.nih.gov/pubmed/35762422 http://dx.doi.org/10.15252/embj.2021109566 |
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author | Das, Aniruddha Thapa, Pankaj Santiago, Ulises Shanmugam, Nilesh Banasiak, Katarzyna Dąbrowska, Katarzyna Nolte, Hendrik Szulc, Natalia A Gathungu, Rose M Cysewski, Dominik Krüger, Marcus Dadlez, Michał Nowotny, Marcin Camacho, Carlos J Hoppe, Thorsten Pokrzywa, Wojciech |
author_facet | Das, Aniruddha Thapa, Pankaj Santiago, Ulises Shanmugam, Nilesh Banasiak, Katarzyna Dąbrowska, Katarzyna Nolte, Hendrik Szulc, Natalia A Gathungu, Rose M Cysewski, Dominik Krüger, Marcus Dadlez, Michał Nowotny, Marcin Camacho, Carlos J Hoppe, Thorsten Pokrzywa, Wojciech |
author_sort | Das, Aniruddha |
collection | PubMed |
description | CHIP (C‐terminus of Hsc70‐interacting protein) and its worm ortholog CHN‐1 are E3 ubiquitin ligases that link the chaperone system with the ubiquitin‐proteasome system (UPS). CHN‐1 can cooperate with UFD‐2, another E3 ligase, to accelerate ubiquitin chain formation; however, the basis for the high processivity of this E3s set has remained obscure. Here, we studied the molecular mechanism and function of the CHN‐1–UFD‐2 complex in Caenorhabditis elegans. Our data show that UFD‐2 binding promotes the cooperation between CHN‐1 and ubiquitin‐conjugating E2 enzymes by stabilizing the CHN‐1 U‐box dimer. However, HSP70/HSP‐1 chaperone outcompetes UFD‐2 for CHN‐1 binding, thereby promoting a shift to the autoinhibited CHN‐1 state by acting on a conserved residue in its U‐box domain. The interaction with UFD‐2 enables CHN‐1 to efficiently ubiquitylate and regulate S‐adenosylhomocysteinase (AHCY‐1), a key enzyme in the S‐adenosylmethionine (SAM) regeneration cycle, which is essential for SAM‐dependent methylation. Our results define the molecular mechanism underlying the synergistic cooperation of CHN‐1 and UFD‐2 in substrate ubiquitylation. |
format | Online Article Text |
id | pubmed-9340540 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-93405402022-08-09 A heterotypic assembly mechanism regulates CHIP E3 ligase activity Das, Aniruddha Thapa, Pankaj Santiago, Ulises Shanmugam, Nilesh Banasiak, Katarzyna Dąbrowska, Katarzyna Nolte, Hendrik Szulc, Natalia A Gathungu, Rose M Cysewski, Dominik Krüger, Marcus Dadlez, Michał Nowotny, Marcin Camacho, Carlos J Hoppe, Thorsten Pokrzywa, Wojciech EMBO J Articles CHIP (C‐terminus of Hsc70‐interacting protein) and its worm ortholog CHN‐1 are E3 ubiquitin ligases that link the chaperone system with the ubiquitin‐proteasome system (UPS). CHN‐1 can cooperate with UFD‐2, another E3 ligase, to accelerate ubiquitin chain formation; however, the basis for the high processivity of this E3s set has remained obscure. Here, we studied the molecular mechanism and function of the CHN‐1–UFD‐2 complex in Caenorhabditis elegans. Our data show that UFD‐2 binding promotes the cooperation between CHN‐1 and ubiquitin‐conjugating E2 enzymes by stabilizing the CHN‐1 U‐box dimer. However, HSP70/HSP‐1 chaperone outcompetes UFD‐2 for CHN‐1 binding, thereby promoting a shift to the autoinhibited CHN‐1 state by acting on a conserved residue in its U‐box domain. The interaction with UFD‐2 enables CHN‐1 to efficiently ubiquitylate and regulate S‐adenosylhomocysteinase (AHCY‐1), a key enzyme in the S‐adenosylmethionine (SAM) regeneration cycle, which is essential for SAM‐dependent methylation. Our results define the molecular mechanism underlying the synergistic cooperation of CHN‐1 and UFD‐2 in substrate ubiquitylation. John Wiley and Sons Inc. 2022-06-28 /pmc/articles/PMC9340540/ /pubmed/35762422 http://dx.doi.org/10.15252/embj.2021109566 Text en © 2022 The Authors. Published under the terms of the CC BY 4.0 license. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Articles Das, Aniruddha Thapa, Pankaj Santiago, Ulises Shanmugam, Nilesh Banasiak, Katarzyna Dąbrowska, Katarzyna Nolte, Hendrik Szulc, Natalia A Gathungu, Rose M Cysewski, Dominik Krüger, Marcus Dadlez, Michał Nowotny, Marcin Camacho, Carlos J Hoppe, Thorsten Pokrzywa, Wojciech A heterotypic assembly mechanism regulates CHIP E3 ligase activity |
title | A heterotypic assembly mechanism regulates CHIP E3 ligase activity |
title_full | A heterotypic assembly mechanism regulates CHIP E3 ligase activity |
title_fullStr | A heterotypic assembly mechanism regulates CHIP E3 ligase activity |
title_full_unstemmed | A heterotypic assembly mechanism regulates CHIP E3 ligase activity |
title_short | A heterotypic assembly mechanism regulates CHIP E3 ligase activity |
title_sort | heterotypic assembly mechanism regulates chip e3 ligase activity |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9340540/ https://www.ncbi.nlm.nih.gov/pubmed/35762422 http://dx.doi.org/10.15252/embj.2021109566 |
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