Assembly status transition offers an avenue for activity modulation of a supramolecular enzyme.
Assembly status transition offers an avenue for activity modulation of a supramolecular enzyme.
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组装状态转换为超分子酶的活性调节提供了途径
DOI：
10.7554/elife.72535
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发表时间：
2021-12-13
期刊：
影响因子：
7.7
通讯作者：
Huang C
中科院分区：
文献类型：
--
作者：
Chen Y;Xu W;Yu S;Ni K;She G;Ye X;Xing Q;Zhao J;Huang C
自然界已经进化出许多超分子蛋白质，它们以某种形态学方式组装在一起，有时甚至看起来过于复杂。这种进化努力背后的基本原理往往知之甚少。在这里，我们提供了原子分辨率的见解如何动态建设的结构复杂的酶与高阶对称性提供顺从复杂的监管。我们已经建立了谷氨酰胺合成酶（GS），一个古老的多亚基酶细胞氮代谢所必需的酶活性和蛋白质形态之间的功能耦合。Cryo-EM结构测定GS在催化活性和非活性组装状态，使我们能够揭示一个意想不到的自组装诱导的无序有序过渡范例，其中两个子复杂实体之间的远程相互作用显着僵化，否则结构波动的活性位点，从而调节活性。我们进一步表明，在体内的证据表明，酶的形态转变可以调节细胞因子的需求。总的来说，我们的数据提供了一个例子，如何组装状态转换提供了一个途径的活动调制，并锐化我们的机械理解的复杂的功能和监管性质的超分子酶。
Nature has evolved many supramolecular proteins assembled in certain, sometimes even seemingly oversophisticated, morphological manners. The rationale behind such evolutionary efforts is often poorly understood. Here, we provide atomic-resolution insights into how the dynamic building of a structurally complex enzyme with higher order symmetry offers amenability to intricate regulation. We have established the functional coupling between enzymatic activity and protein morphological states of glutamine synthetase (GS), an old multi-subunit enzyme essential for cellular nitrogen metabolism. Cryo-EM structure determination of GS in both the catalytically active and inactive assembly states allows us to reveal an unanticipated self-assembly-induced disorder-order transition paradigm, in which the remote interactions between two subcomplex entities significantly rigidify the otherwise structurally fluctuating active sites, thereby regulating activity. We further show in vivo evidences that how the enzyme morphology transitions could be modulated by cellular factors on demand. Collectively, our data present an example of how assembly status transition offers an avenue for activity modulation, and sharpens our mechanistic understanding of the complex functional and regulatory properties of supramolecular enzymes.