Atomistic Mechanism of Force Generation, Translocation, and Coordination in a Viral Genome Packaging Motor
Atomistic Mechanism of Force Generation, Translocation, and Coordination in a Viral Genome Packaging Motor
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病毒基因组包装电机中力产生、易位和协调的原子机制
DOI：
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
M. Morais
中科院分区：
文献类型：
--
作者：
Joshua Pajak;E. Dill;M. A. White;B. Kelch;P. Jardine;G. Arya;M. Morais
双链 DNA 病毒使用病毒编码的 ATP 酶环形马达将其基因组包装到预组装的蛋白质衣壳中。虽然从这些马达中分离出来的单体（亚基）的几种结构已经确定，但它们对功能环内的亚基如何协调其活动以有效产生力和易位 DNA 的了解很少。在这里，我们描述了病毒 DNA 包装马达功能环形式的第一个原子分辨率结构，并通过长时间尺度分子动力学模拟表征其原子级动力学。噬菌体 asccφ28 的五聚体 ATP 酶环的晶体结构表明，每个亚基由一个规范的 N 端 ASCE ATP 酶结构域组成，通过一个小盖子结构域与“残留”核酸酶结构域相连。盖子子结构域封闭 ATP 酶活性位点，并与邻近的亚基进行广泛的相互作用，从而使几个重要的催化残基定位在反式中发挥作用。环的孔内排列着几个可与 DNA 相互作用的带正电荷的残基。对 ATP 酶环在各种核苷酸结合状态下的模拟提供了有关电机如何协调环周围顺序核苷酸结合、水解和交换的信息。模拟还预测该环采用螺旋结构来追踪 DNA，这与最近对 φ29 包装 ATP 酶的冷冻电镜重建一致。基于这些结果，提出了病毒 DNA 包装的原子模型，其中 DNA 易位由逐步螺旋到平面环转变提供动力，这些转变通过 ATP 结合、水解和释放紧密协调。
Double-stranded DNA viruses package their genomes into pre-assembled protein capsids using virally-encoded ATPase ring motors. While several structures of isolated monomers (subunits) from these motors have been determined, they provide little insight into how subunits within a functional ring coordinate their activities to efficiently generate force and translocate DNA. Here we describe the first atomic-resolution structure of a functional ring form of a viral DNA packaging motor and characterize its atomic-level dynamics via long timescale molecular dynamics simulations. Crystal structures of the pentameric ATPase ring from bacteriophage asccφ28 show that each subunit consists of a canonical N-terminal ASCE ATPase domain connected to a ‘vestigial’ nuclease domain by a small lid subdomain. The lid subdomain closes over the ATPase active site and engages in extensive interactions with a neighboring subunit such that several important catalytic residues are positioned to function in trans. The pore of the ring is lined with several positively charged residues that can interact with DNA. Simulations of the ATPase ring in various nucleotide-bound states provide information about how the motor coordinates sequential nucleotide binding, hydrolysis, and exchange around the ring. Simulations also predict that the ring adopts a helical structure to track DNA, consistent with recent cryo-EM reconstruction of the φ29 packaging ATPase. Based on these results, an atomistic model of viral DNA packaging is proposed wherein DNA translocation is powered by stepwise helical-to-planar ring transitions that are tightly coordinated by ATP binding, hydrolysis, and release.
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影响因子：
5.7
作者：
Morais, Marc C.;Koti, Jaya S.;Bowman, Valorie D.;Reyes-Aldrete, Emilio;Anderson, Dwight L.;Rossmann, Michael G.
通讯作者：
Rossmann, Michael G.
影响因子：
5.6
作者：
Fuller, Derek N.;Raymer, Dorian M.;Smith, Doucilas E.
通讯作者：
Smith, Doucilas E.
NBD1的Walker A基序中S685的羟基和Walker B基序中D792的羧基对于多药耐药蛋白的折叠和功能起着至关重要的作用。
DOI：
10.1016/j.bbamem.2007.11.010
发表时间：
2008
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Yang,Runying;Scavetta,Robert;Chang,Xiu-Bao
通讯作者：
Chang,Xiu-Bao
影响因子：
11.3
作者：
Rao VB;Feiss M
通讯作者：
Feiss M
影响因子：
3
作者：
Ogura, T;Whiteheart, SW;Wilkinson, AJ
通讯作者：
Wilkinson, AJ