Structural highlights
Publication Abstract from PubMed
Homologous to E6-AP C terminus (HECT) E3 ligases recognize and directly catalyze ligation of ubiquitin (Ub) to their substrates. Molecular details of this process remain unknown. We report the first structure, to our knowledge, of a Ub-loaded E3, the human neural precursor cell-expressed developmentally downregulated protein 4 (Nedd4). The HECTNedd4~Ub transitory intermediate provides a structural basis for the proposed sequential addition mechanism. The donor Ub, transferred from the E2, is bound to the Nedd4 C lobe with its C-terminal tail locked in an extended conformation, primed for catalysis. We provide evidence that the Nedd4-family members are Lys63-specific enzymes whose catalysis is mediated by an essential C-terminal acidic residue.
Structure of a ubiquitin-loaded HECT ligase reveals the molecular basis for catalytic priming.,Maspero E, Valentini E, Mari S, Cecatiello V, Soffientini P, Pasqualato S, Polo S Nat Struct Mol Biol. 2013 May 5. doi: 10.1038/nsmb.2566. PMID:23644597[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Maspero E, Valentini E, Mari S, Cecatiello V, Soffientini P, Pasqualato S, Polo S. Structure of a ubiquitin-loaded HECT ligase reveals the molecular basis for catalytic priming. Nat Struct Mol Biol. 2013 May 5. doi: 10.1038/nsmb.2566. PMID:23644597 doi:10.1038/nsmb.2566
