Kulathu Yogesh, Akutsu Masato, Bremm Anja, Hofmann Kay, Komander David
Medical Research Council Laboratory of Molecular Biology, Cambridge, UK.
Nat Struct Mol Biol. 2009 Dec;16(12):1328-30. doi: 10.1038/nsmb.1731. Epub 2009 Nov 22.
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.
蛋白激酶TAK1通过其亚基TAB2与赖氨酸63（K63）连接的泛素链结合而被激活。在此，我们分析了与K63连接的二聚泛素和三聚泛素结合的TAB2 NZF结构域的晶体结构，结果表明，TAB2通过两个不同的结合位点与相邻的泛素部分结合。TAB2对K63二聚体施加的构象限制不能被线性链采用，这解释了为什么TAK1不能被线性泛素化事件激活。
