Completion of the Vimentin Rod Domain Structure Using Experimental Restraints: A New Tool for Exploring Intermediate Filament Assembly and Mutations
Completion of the Vimentin Rod Domain Structure Using Experimental Restraints: A New Tool for Exploring Intermediate Filament Assembly and Mutations
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DOI：
10.1016/j.str.2019.07.011
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发表时间：
2019-10-01
期刊：
影响因子：
5.7
通讯作者：
Voss, John C.
中科院分区：
文献类型：
--
作者：
Gae, David D.;Budamagunta, Madhu S.;Voss, John C.
全长波形蛋白的电子顺磁共振（EPR）光谱和波形蛋白肽的X-射线晶体学提供了一致的结构数据，几乎整个中心杆域的蛋白质。在这份报告中，我们使用EPR光谱和分子建模的组合来确定缺失区域的结构和动力学，并将单独的元素合并为一个结构。验证的链接器1-2（L1-2）建模方法证明了EPR和X射线数据在以前解决的地区之间的密切相关性。重要的是，分子动力学（MD）模拟所构建的模型同意由EPR确定的自旋标记运动。此外，分子动力学模拟显示L1-2异质性，与二聚体链之间的状态的协调切换。这些数据提供了有史以来第一个完整的中间丝杆域的实验驱动模型，为进一步的建模和组装研究提供了研究工具。
Electron paramagnetic resonance (EPR) spectroscopy of full-length vimentin and X-ray crystallography of vimentin peptides has provided concordant structural data for nearly the entire central rod domain of the protein. In this report, we use a combination of EPR spectroscopy and molecular modeling to determine the structure and dynamics of the missing region and unite the separate elements into a single structure. Validation of the linker 1-2 (L1-2) modeling approach is demonstrated by the close correlation between EPR and X-ray data in the previously solved regions. Importantly, molecular dynamic (MD) simulation of the constructed model agrees with spin label motion as determined by EPR. Furthermore, MD simulation shows L1-2 heterogeneity, with a concerted switching of states among the dimer chains. These data provide the first ever experimentally driven model of a complete intermediate filament rod domain, providing research tools for further modeling and assembly studies.