Park Young Bong, Hohl Marcel, Padjasek Michał, Jeong Eunyoung, Jin Kyeong Sik, Krężel Artur, Petrini John H J, Cho Yunje
Department of Life Sciences, Pohang University of Science and Technology, Pohang, South Korea.
Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
Nat Struct Mol Biol. 2017 Mar;24(3):248-257. doi: 10.1038/nsmb.3369. Epub 2017 Jan 30.
The Rad50 hook interface is crucial for assembly and various functions of the Mre11 complex. Previous analyses suggested that Rad50 molecules interact within (intracomplex) or between (intercomplex) dimeric complexes. In this study, we determined the structure of the human Rad50 hook and coiled-coil domains. The data suggest that the predominant structure is the intracomplex, in which the two parallel coiled coils proximal to the hook form a rod shape, and that a novel interface within the coiled-coil domains of Rad50 stabilizes the interaction of Rad50 protomers in the dimeric assembly. In yeast, removal of the coiled-coil interface compromised Tel1 activation without affecting DNA repair, while simultaneous disruption of that interface and the hook phenocopied a null mutation. The results demonstrate that the hook and coiled-coil interfaces coordinately promote intracomplex assembly and define the intracomplex as the functional form of the Mre11 complex.
Rad50钩状结构域对于Mre11复合体的组装和多种功能至关重要。先前的分析表明，Rad50分子在二聚体复合物内部（复合体内）或之间（复合体间）相互作用。在本研究中，我们确定了人类Rad50钩状结构域和卷曲螺旋结构域的结构。数据表明，主要结构是复合体内结构，其中靠近钩状结构域的两条平行卷曲螺旋形成杆状，并且Rad50卷曲螺旋结构域内的一个新界面稳定了二聚体组装中Rad50原聚体的相互作用。在酵母中，去除卷曲螺旋界面会损害Tel1激活但不影响DNA修复，而同时破坏该界面和钩状结构域则模拟了无效突变。结果表明，钩状结构域和卷曲螺旋界面协同促进复合体内组装，并将复合体内结构定义为Mre11复合体的功能形式。
