Molecular recognition and deubiquitination of cyclic K48-linked ubiquitin chains by OTUB1.
Biochem Biophys Res Commun
; 562: 94-99, 2021 07 12.
Article
en En
| MEDLINE
| ID: mdl-34049206
ABSTRACT
Conjugation of K48-linked ubiquitin chains to intracellular proteins mainly functions as a signal for proteasomal degradation. The conjugating enzyme E2-25K synthesizes not only canonical (noncyclic) but also cyclic K48-linked ubiquitin chains. Although the cyclic conformation is expected to repress molecular recognition by ubiquitin binding proteins due to restricting the flexibility of the ubiquitin subunits in a chain, multiple proteins are reported to associate with cyclic ubiquitin chains similar to noncyclic chains. However, the molecular mechanism of how cyclic ubiquitin chains are recognized remains unclear. Here we investigated the effect of cyclization on ubiquitin-chain cleavage and molecular recognition by a K48-linkage specific deubiquitinating enzyme OTUB1 for cyclic diubiquitin by NMR spectroscopic analyses. Compared to noncyclic diubiquitin, we observed slow but unambiguously detectable cleavage of cyclic diubiquitin to monoubiquitin by OTUB1. Intriguingly, upon ubiquitin chain cleavage, cyclic diubiquitin appeared to alter its "autoinhibited" conformation to an incompletely but partially accessible conformation, induced by interaction with OTUB1 via the ubiquitin-subunit specific recognition patches and adjacent surfaces. These data imply that cyclic ubiquitin chains may exist stably in cells in spite of the presence of deubiquitinating enzymes and that these chains can be recognized by intracellular proteins in a manner distinct from that of noncyclic ubiquitin chains.
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Texto completo:
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Base de datos:
MEDLINE
Asunto principal:
Ubiquitina
/
Ubiquitinación
/
Enzimas Desubicuitinizantes
/
Lisina
Límite:
Humans
Idioma:
En
Revista:
Biochem Biophys Res Commun
Año:
2021
Tipo del documento:
Article
País de afiliación:
Japón