RBR E3-ligases at work.
The RING-in-between-RING (RBR) E3s are a curious family of ubiquitin E3-ligases, whose mechanism of action is unusual in several ways. Their activities are auto-inhibited, causing a requirement for activation by protein-protein interactions or posttranslational modifications. They catalyse ubiquitin conjugation by a concerted RING/HECT-like mechanism in which the RING1 domain facilitates E2-discharge to directly form a thioester intermediate with a cysteine in RING2. This short-lived, HECT-like intermediate then modifies the target. Uniquely, the RBR ligase HOIP makes use of this mechanism to target the ubiquitin amino-terminus, by presenting the target ubiquitin for modification using its distinctive LDD region.
Division of Biochemistry and Cancer Genomics Centre, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Judith J
JJ
Smit
Titia K
TK
Sixma
D000595:Amino Acid Sequence; D000818:Animals; D020134:Catalytic Domain; D006801:Humans; D008969:Molecular Sequence Data; D054829:RING Finger Domains; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry / Q000378:metabolism*
D044767:Ubiquitin-Protein Ligases