Crystal Structure of Entamoeba histolytica Cdc45 Suggests a Conformational Switch that May Regulate DNA Replication.
Crystal Structure of Entamoeba histolytica Cdc45 Suggests a Conformational Switch that May Regulate DNA Replication.
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Entamoeba Histolictica cdc45的晶体结构提出了一种可能调节DNA复制的构象开关。
DOI：
10.1016/j.isci.2018.04.011
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发表时间：
2018-05-25
期刊：
影响因子：
5.8
通讯作者：
Aihara H
中科院分区：
文献类型：
--
作者：
Kurniawan F;Shi K;Kurahashi K;Bielinsky AK;Aihara H
Cdc 45在真核DNA复制体的核心中起关键作用，作为复制解旋酶全酶Cdc 45-MCM-GINS（CMG）复合物的重要支架组分。来自溶组织内阿米巴的全长Cdc 45蛋白质的1.66 μ m分辨率晶体结构显示出与先前在其活性构象中观察到的人Cdc 45相似的蛋白质折叠，其特征在于整体盘状单体形状和N-和C-末端DHH结构域之间的紧密接触。然而，溶组织艾美耳球虫Cdc 45结构显示出几个独特的特征，包括C-末端DHHA 1结构域的不同取向，与DNA聚合酶β相互作用有关的相邻突出α-螺旋片段的伴随无序，以及GINS/Mcm 5结合环的独特构象。这些结构观察共同表明Cdc 45可以对对应于不同功能状态的多种构象进行采样的可能性。我们认为Cdc 45的这种构象转换可能允许调节DNA复制中重要的蛋白质-蛋白质相互作用。全长Cdc 45蛋白质的高分辨率晶体结构独特的蛋白质构象缺乏α-螺旋突起C-末端DHHA 1结构域的独特定位可能与MCM结合偶联一个构象开关可以调节Cdc 45的DNA聚合酶相互作用生物物理学;蛋白质结构方面;结构生物学
Cdc45 plays a critical role at the core of the eukaryotic DNA replisome, serving as an essential scaffolding component of the replicative helicase holoenzyme Cdc45-MCM-GINS (CMG) complex. A 1.66-Å-resolution crystal structure of the full-length Cdc45 protein from Entamoeba histolytica shows a protein fold similar to that observed previously for human Cdc45 in its active conformation, featuring the overall disk-like monomer shape and intimate contacts between the N- and C-terminal DHH domains. However, the E. histolytica Cdc45 structure shows several unique features, including a distinct orientation of the C-terminal DHHA1 domain, concomitant disordering of the adjacent protruding α-helical segment implicated in DNA polymerase ɛ interactions, and a unique conformation of the GINS/Mcm5-binding loop. These structural observations collectively suggest the possibility that Cdc45 can sample multiple conformations corresponding to different functional states. We propose that such conformational switch of Cdc45 may allow regulation of protein-protein interactions important in DNA replication. High-resolution crystal structure of a full-length Cdc45 protein Distinct protein conformation lacking the α-helical protrusion Unique positioning of the C-terminal DHHA1 domain possibly coupled to MCM binding A conformational switch may regulate DNA polymerase ɛ interactions of Cdc45 Biophysics; Protein Structure Aspects; Structural Biology
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DOI：
10.1073/pnas.1700530114
发表时间：
2017-04-18
影响因子：
11.1
作者：
Zhou, Jin Chuan;Janska, Agnieszka;Costa, Alessandro
通讯作者：
Costa, Alessandro
影响因子：
16.6
作者：
Simon AC;Sannino V;Costanzo V;Pellegrini L
通讯作者：
Pellegrini L
影响因子：
16.8
作者：
Sun J;Shi Y;Georgescu RE;Yuan Z;Chait BT;Li H;O'Donnell ME
通讯作者：
O'Donnell ME
影响因子：
14.9
作者：
Oyama T;Ishino S;Shirai T;Yamagami T;Nagata M;Ogino H;Kusunoki M;Ishino Y
通讯作者：
Ishino Y
影响因子：
7.5
作者：
Boos, Dominik;Frigola, Jordi;Diffley, John F. X.
通讯作者：
Diffley, John F. X.