The structure of the FANCM-MHF complex reveals physical features for functional assembly.
The structure of the FANCM-MHF complex reveals physical features for functional assembly.
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FANCM-MHF复合物的结构揭示了功能组装的物理特征
DOI：
10.1038/ncomms1779
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发表时间：
2012-04-17
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
--
作者：
范可尼贫血是一种罕见的遗传性疾病，其特征是染色体不稳定和癌症易感性。范可尼贫血互补组蛋白M （FANCM）与MHF1/MHF2（含组蛋白折叠蛋白）形成一种进化保守的DNA加工复合物，这对于基因毒性应激反应中的DNA修复至关重要。在这里，我们展示了MHF1-MHF2复合物单独结合到FANCM片段（FANCM661−800，命名为FANCM- f）的晶体结构。结构表明MHF1和MHF2形成紧密的四聚体，FANCM-F通过“双v”形结构与之结合。FANCM-F和（MHF1-MHF2）2合作构成一个新的dna结合位点，与典型的L1L2区偶联。MHF-FANCM-F结构塑性的扰动改变了FANCM在体内的定位。MHF-FANCM相互作用及其亚细胞定位被FANCM疾病相关突变体改变。这些发现揭示了MHF-FANCM识别的分子基础，并为导致范可尼贫血的途径提供了机制见解。范可尼贫血的特点是无法修复DNA损伤，并与范可尼贫血核复合体的突变有关，其中包括蛋白FANCM。本研究报道了FANCM与含组蛋白复合物MHF1-MHF2结合的片段的晶体结构。
Fanconi anaemia is a rare genetic disease characterized by chromosomal instability and cancer susceptibility. The Fanconi anaemia complementation group protein M (FANCM) forms an evolutionarily conserved DNA-processing complex with MHF1/MHF2 (histone-fold-containing proteins), which is essential for DNA repair in response to genotoxic stress. Here we present the crystal structures of the MHF1–MHF2 complex alone and bound to a fragment of FANCM (FANCM661−800, designated FANCM-F). The structures show that MHF1 and MHF2 form a compact tetramer to which FANCM-F binds through a 'dual-V' shaped structure. FANCM-F and (MHF1–MHF2)2 cooperate to constitute a new DNA-binding site that is coupled to the canonical L1L2 region. Perturbation of the MHF–FANCM-F structural plasticity changes the localization of FANCM in vivo. The MHF–FANCM interaction and its subcellular localization are altered by a disease-associated mutant of FANCM. These findings reveal the molecular basis of MHF–FANCM recognition and provide mechanistic insights into the pathway leading to Fanconi anaemia. Fanconi's anaemia is characterized by an inability to repair DNA damage and is associated with mutations in the Fanconi anaemia nuclear complex, which includes the protein FANCM. This study reports the crystal structures of a fragment of FANCM bound to the histone-fold-containing protein complex, MHF1–MHF2.
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影响因子：
30.8
作者：
Kim, Yonghwan;Lach, Francis P.;Desetty, Rohini;Hanenberg, Helmut;Auerbach, Arleen D.;Smogorzewska, Agata
通讯作者：
Smogorzewska, Agata
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
64.5
作者：
Kratz, Katja;Schoepf, Barbara;Jiricny, Josef
通讯作者：
Jiricny, Josef
CENP-U 与 Hec1 合作协调动粒-微管附着
影响因子：
4.8
作者：
Hua, Shasha;Wang, Zhikai;Yao, Xuebiao
通讯作者：
Yao, Xuebiao
影响因子：
16
作者：
Gari, Kerstin;Decaillet, Chantal;Constantinou, Angelos
通讯作者：
Constantinou, Angelos