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Solid-state NMR structures of integral membrane proteins.
Molecular Membrane Biology ( IF 2.857 ) Pub Date : 2016-02-08 , DOI: 10.3109/09687688.2016.1139754
Simon G Patching 1
Affiliation  

Solid-state NMR is unique for its ability to obtain three-dimensional structures and to measure atomic-resolution structural and dynamic information for membrane proteins in native lipid bilayers. An increasing number and complexity of integral membrane protein structures have been determined by solid-state NMR using two main methods. Oriented sample solid-state NMR uses macroscopically aligned lipid bilayers to obtain orientational restraints that define secondary structure and global fold of embedded peptides and proteins and their orientation and topology in lipid bilayers. Magic angle spinning (MAS) solid-state NMR uses unoriented rapidly spinning samples to obtain distance and torsion angle restraints that define tertiary structure and helix packing arrangements. Details of all current protein structures are described, highlighting developments in experimental strategy and other technological advancements. Some structures originate from combining solid- and solution-state NMR information and some have used solid-state NMR to refine X-ray crystal structures. Solid-state NMR has also validated the structures of proteins determined in different membrane mimetics by solution-state NMR and X-ray crystallography and is therefore complementary to other structural biology techniques. By continuing efforts in identifying membrane protein targets and developing expression, isotope labelling and sample preparation strategies, probe technology, NMR experiments, calculation and modelling methods and combination with other techniques, it should be feasible to determine the structures of many more membrane proteins of biological and biomedical importance using solid-state NMR. This will provide three-dimensional structures and atomic-resolution structural information for characterising ligand and drug interactions, dynamics and molecular mechanisms of membrane proteins under physiological lipid bilayer conditions.



中文翻译:

完整膜蛋白的固态NMR结构。

固态NMR的独特之处在于它能够获得三维结构,并能够测量天然脂质双层中膜蛋白的原子分辨率结构和动态信息。使用两种主要方法,通过固态NMR已确定了越来越多的复杂膜蛋白结构,且结构复杂。定向样品固态NMR使用宏观排列的脂质双层来获得定向限制,这些限制限定了嵌入的肽和蛋白质的二级结构和整体折叠以及它们在脂质双层中的定向和拓扑。魔角旋转(MAS)固态NMR使用未取向的快速旋转样品来获得距离和扭转角约束,从而限制了三级结构和螺旋堆积的排列方式。描述了所有当前蛋白质结构的详细信息,重点介绍实验策略和其他技术进步方面的发展。一些结构源自固态和溶液态NMR信息的结合,而某些结构已使用固态NMR来细化X射线晶体结构。固态NMR还通过溶液态NMR和X射线晶体学验证了在不同膜模拟物中确定的蛋白质结构,因此可与其他结构生物学技术互补。通过继续努力确定膜蛋白靶标并开发表达,同位素标记和样品制备策略,探针技术,NMR实验,计算和建模方法以及与其他技术的结合,确定更多生物膜蛋白的结构应该是可行的。和使用固态NMR的生物医学重要性。

更新日期:2016-02-08
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