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Structure of the HECT:ubiquitin complex and its role in ubiquitin chain elongation
Author(s) -
Maspero Elena,
Mari Sara,
Valentini Eleonora,
Musacchio Andrea,
Fish Alexander,
Pasqualato Sebastiano,
Polo Simona
Publication year - 2011
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/embor.2011.21
Subject(s) - ubiquitin , nedd4 , ubiquitin ligase , deubiquitinating enzyme , processivity , substrate (aquarium) , microbiology and biotechnology , chemistry , ubiquitin protein ligases , biochemistry , biology , enzyme , gene , ecology , polymerase
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.