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

Elena Maspero, Sara Mari, Eleonora Valentini, Andrea Musacchio, Alexander Fish, Sebastiano Pasqualato, Simona Polo

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)342-349
Number of pages8
JournalEMBO Reports
Volume12
Issue number4
DOIs
Publication statusPublished - Apr 1 2011

Keywords

  • catalysis
  • E3 ligase
  • polyubiquitination
  • structure
  • ubiquitin

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Biochemistry

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