title: Two-sided ubiquitin binding explains specificity of the TAB2 NZF domain.
abstract: The protein kinase TAK1 is activated by binding to Lys63 (K63)-linked ubiquitin chains through its subunit TAB2. Here we analyze crystal structures of the TAB2 NZF domain bound to Lys63-linked di- and triubiquitin, revealing that TAB2 binds adjacent ubiquitin moieties via two distinct binding sites. The conformational constraints imposed by TAB2 on a Lys63 dimer cannot be adopted by linear chains, explaining why TAK1 cannot be activated by linear ubiquitination events.
authors: Medical Research Council Laboratory of Molecular Biology, Cambridge, UK.
authors: Yogesh
authors: Y
authors: Kulathu
authors: Masato
authors: M
authors: Akutsu
authors: Anja
authors: A
authors: Bremm
authors: Kay
authors: K
authors: Hofmann
authors: David
authors: D
authors: Komander
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry* / Q000378:metabolism*; D000595:Amino Acid Sequence; D001665:Binding Sites; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D008969:Molecular Sequence Data; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D013379:Substrate Specificity; D025801:Ubiquitin / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C410585:TAB2 protein, human; D025801:Ubiquitin