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Different HECT domain ubiquitin ligases employ distinct mechanisms of polyubiquitin chain synthesis
Author(s) -
Wang Min,
Pickart Cecile M
Publication year - 2005
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7600895
Subject(s) - biology , ubiquitin , ubiquitin protein ligases , chain (unit) , domain (mathematical analysis) , microbiology and biotechnology , ubiquitin ligase , posttranslational modification , computational biology , genetics , biochemistry , gene , enzyme , mathematical analysis , mathematics , physics , astronomy
Individual ubiquitin (Ub)–protein ligases (E3s) cooperate with specific Ub‐conjugating enzymes (E2s) to modify cognate substrates with polyubiquitin chains. E3s belonging to the Really Interesting New Gene (RING) and Homologous to E6‐Associated Protein (E6AP) C‐Terminus (HECT) domain families utilize distinct molecular mechanisms. In particular, HECT E3s, but not RING E3s, form a thiol ester with Ub before transferring Ub to the substrate lysine. Here we report that different HECT domain E3s can employ distinct mechanisms of polyubiquitin chain synthesis. We show that E6AP builds up a K48‐linked chain on its HECT cysteine residue, while KIAA10 builds up K48‐ and K29‐linked chains as free entities. A small region near the N‐terminus of the conserved HECT domain helps to bring about this functional distinction. Thus, a given HECT domain can specify both the linkage of a polyubiquitin chain and the mechanism of its assembly.