组蛋白伴侣RbAp46识别组蛋白H4的结构基础。
Structural basis for the recognition of histone H4 by the histone-chaperone RbAp46.
作者信息
Murzina Natalia V, Pei Xue-Yuan, Zhang Wei, Sparkes Mike, Vicente-Garcia Jose, Pratap J Venkatesh, McLaughlin Stephen H, Ben-Shahar Tom Rolef, Verreault Alain, Luisi Ben F, Laue Ernest D
机构信息
Department of Biochemistry, 80 Tennis Court Road, Cambridge CB2 1GA, UK.
出版信息
Structure. 2008 Jul;16(7):1077-85. doi: 10.1016/j.str.2008.05.006. Epub 2008 Jun 19.
RbAp46 and RbAp48 (pRB-associated proteins p46 and p48, also known as RBBP7 and RBBP4, respectively) are highly homologous histone chaperones that play key roles in establishing and maintaining chromatin structure. We report here the crystal structure of human RbAp46 bound to histone H4. RbAp46 folds into a seven-bladed beta propeller structure and binds histone H4 in a groove formed between an N-terminal alpha helix and an extended loop inserted into blade six. Surprisingly, histone H4 adopts a different conformation when interacting with RbAp46 than it does in either the nucleosome or in the complex with ASF1, another histone chaperone. Our structural and biochemical results suggest that when a histone H3/H4 dimer (or tetramer) binds to RbAp46 or RbAp48, helix 1 of histone H4 unfolds to interact with the histone chaperone. We discuss the implications of our findings for the assembly and function of RbAp46 and RbAp48 complexes.
RbAp46和RbAp48（与视网膜母细胞瘤蛋白相关的蛋白质p46和p48，也分别称为RBBP7和RBBP4）是高度同源的组蛋白伴侣，在建立和维持染色质结构中起关键作用。我们在此报告了与组蛋白H4结合的人RbAp46的晶体结构。RbAp46折叠成七叶β螺旋桨结构，并在N端α螺旋和插入到第六叶片的延伸环之间形成的凹槽中结合组蛋白H4。令人惊讶的是，组蛋白H4与RbAp46相互作用时所采用的构象不同于其在核小体中或与另一种组蛋白伴侣ASF1形成的复合物中的构象。我们的结构和生化结果表明，当组蛋白H3/H4二聚体（或四聚体）与RbAp46或RbAp48结合时，组蛋白H4的螺旋1会展开以与组蛋白伴侣相互作用。我们讨论了我们的发现对RbAp46和RbAp48复合物的组装和功能的影响。
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