The RNA-Binding Site of Poliovirus 3C Protein Doubles as a Phosphoinositide-Binding Domain.
The RNA-Binding Site of Poliovirus 3C Protein Doubles as a Phosphoinositide-Binding Domain.
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DOI：
10.1016/j.str.2017.11.001
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发表时间：
2017-12-05
期刊：
影响因子：
--
通讯作者：
Cameron CE
中科院分区：
文献类型：
--
作者：
Shengjuler D;Chan YM;Sun S;Moustafa IM;Li ZL;Gohara DW;Buck M;Cremer PS;Boehr DD;Cameron CE
一些病毒使用磷脂酰肌醇磷酸(PIP)来标记用于基因组复制或病毒粒子组装的膜。病毒蛋白中不存在细胞蛋白的PIP结合基序。分子对接模拟揭示了PIP与脊髓灰质炎病毒(PV)3C蛋白结合的假定位置，并通过核磁共振光谱进行了验证。PIP结合位点位于一个高度动态的α螺旋上，该螺旋也具有与RNA结合的功能。使用荧光偏振分析在溶液中观察到广泛的PIP结合活性，或者使用芯片上的荧光分析在脂质双层的背景下观察到广泛的PIP结合活性。对3C蛋白-膜界面的全原子分子动力学模拟揭示了PIP的聚集和可能依赖于PIP的构象。PIP聚簇是通过与与RNA磷酸二酯骨架相互作用的残基相互作用而介导的。我们的结论是，3C与膜的结合将由PIP的丰度决定。我们认为，观察到的3C功能的二重性可能延伸到其他病毒的RNA结合蛋白。病毒的PIP结合部位与已知的RNA结合部位重叠，PIP结合部位聚集PIP，并可能调节PIP和RNA结合部位的构象和功能二重性可能延伸到其他病毒。病毒蛋白中缺乏传统的PIP结合结构域，为解决这一问题提供了独特的结构性解决方案。盛居乐等人。表明病毒RNA结合位点可以被重新用于PIP结合。可以实现PIP集群。PIP的性质可能调节蛋白质的构象。
Some viruses use phosphatidylinositol phosphate (PIP) to mark membranes used for genome replication or virion assembly. PIP-binding motifs of cellular proteins do not exist in viral proteins. Molecular-docking simulations revealed a putative site of PIP binding to poliovirus (PV) 3C protein that was validated using nuclear magnetic resonance spectroscopy. The PIP-binding site was located on a highly dynamic α helix, which also functions in RNA binding. Broad PIP-binding activity was observed in solution using a fluorescence polarization assay or in the context of a lipid bilayer using an on-chip, fluorescence assay. All-atom molecular dynamics simulations of the 3C protein-membrane interface revealed PIP clustering and perhaps PIP-dependent conformations. PIP clustering was mediated by interaction with residues that interact with the RNA phosphodiester backbone. We conclude that 3C binding to membranes will be determined by PIP abundance. We suggest that the duality of function observed for 3C may extend to RNA-binding proteins of other viruses. A viral PIP-binding site identified, validated, and characterized PIP-binding site overlaps the known RNA-binding site PIP-binding site clusters PIPs and perhaps regulates conformation and function Duality of PIP- and RNA-binding sites may extend to other viruses The absence of conventional PIP-binding domains in viral proteins suggests unique structural solutions to this problem. Shengjuler et al. show that a viral RNA-binding site can be repurposed for PIP binding. PIP clustering can be achieved. The nature of the PIP may regulate protein conformation.
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冠状病毒主蛋白酶的结构揭示了甲over依蛋白酶折叠与额外的α-螺旋结构域的组合。
影响因子：
11.4
作者：
Anand, Kanchan;Palm, Gottfried J;Mesters, Jeroen R;Siddell, Stuart G;Ziebuhr, John;Hilgenfeld, Rolf
通讯作者：
Hilgenfeld, Rolf
影响因子：
3.3
作者：
Klauda, Jeffery B.;Venable, Richard M.;Freites, J. Alfredo;O'Connor, Joseph W.;Tobias, Douglas J.;Mondragon-Ramirez, Carlos;Vorobyov, Igor;MacKerell, Alexander D., Jr.;Pastor, Richard W.
通讯作者：
Pastor, Richard W.
影响因子：
4.6
作者：
Johnson KA;Taghon GJ;Scott JL;Stahelin RV
通讯作者：
Stahelin RV
影响因子：
3.1
作者：
Cameron CE;Oh HS;Moustafa IM
通讯作者：
Moustafa IM
影响因子：
7.4
作者：
Huang, Da;Zhao, Tao;Cremer, Paul S.
通讯作者：
Cremer, Paul S.