Structure of the HECT:ubiquitin complex and its role in ubiquitin chain elongation

Several mechanisms have been proposed for the synthesis of substrate‐linked ubiquitin chains. HECT ligases directly catalyse protein ubiquitination and have been found to non‐covalently interact with ubiquitin. We report crystal structures of the Nedd4 HECT domain, alone and in complex with ubiquitin, which show a new binding mode involving two surfaces on ubiquitin and both subdomains of the HECT N‐lobe. The structures suggest a model for HECT‐to‐substrate ubiquitin transfer, in which the growing chain on the substrate is kept close to the catalytic cysteine to promote processivity. Mutational analysis highlights differences between the processes of substrate polyubiquitination and self‐ubiquitination.
Analysis of ubiquitin binding to the HECT domain of Nedd4 suggests that the ubiquitin chain being elongated is kept close to the catalytic cysteine to promote processivity. Together with the accompanying paper by the Huibregtse group, this study shows the catalysis of polyubiquitin chains by HECT E3 ligases.

Object Details

• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch

References and Relationships

• Bibliographic citation: Structure of the HECT:ubiquitin complex and its role in ubiquitin chain elongation ; volume:12 ; number:4 ; year:2011 ; pages:342-349 ; extent:8 ; EMBO reports / European Molecular Biology Organization ; 12, Heft 4 (2011), 342-349 (gesamt 8)

Contributors, Places and Time

• Creator: Maspero, Elena ; Mari, Sara ; Valentini, Eleonora ; Musacchio, Andrea ; Fish, Alexander ; Pasqualato, Sebastiano ; Polo, Simona

Further information

• DOI: 10.1038/embor.2011.21
• URN: urn:nbn:de:101:1-2023032106493452090164
• Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 14.08.2025, 10:47 AM CEST