Relaxation dispersion NMR spectroscopy for the study of protein allostery.
Relaxation dispersion NMR spectroscopy for the study of protein allostery.
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DOI：
10.1007/s12551-015-0166-6
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发表时间：
2015-06-01
影响因子：
--
通讯作者：
Mittermaier, Anthony
中科院分区：
文献类型：
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作者：
Farber, Patrick J;Mittermaier, Anthony
在生物大分子中的远距离位点之间的信息的变构传递通常涉及活性构象和非活性构象之间的集体转变。核磁共振（NMR）光谱可以产生这些动力学的详细信息。特别是，弛豫分散技术提供的结构，动态和机制的信息发生在毫秒到微秒的时间尺度上的构象转变。在这篇综述中，我们提供了一个概述的理论和分析的Carr-Purcell-Meiboom-Gill（CPMG）弛豫色散NMR实验，并简要描述其应用于研究的变构动力学的同源结构域从PBX转录因子（PBX-HD）。CPMG NMR数据表明，PBX-HD的一部分中的局部折叠（螺旋/卷曲）转变有助于在两个遥远的结合位点之间传递信息。此外，CPMG和其他自旋弛豫数据的组合表明，该区域也可以进行局部错误折叠，让人想起构象系综模型的变构。
Allosteric transmission of information between distant sites in biological macromolecules often involves collective transitions between active and inactive conformations. Nuclear magnetic resonance (NMR) spectroscopy can yield detailed information on these dynamics. In particular, relaxation dispersion techniques provide structural, dynamic, and mechanistic information on conformational transitions occurring on the millisecond to microsecond timescales. In this review, we provide an overview of the theory and analysis of Carr-Purcell-Meiboom-Gill (CPMG) relaxation dispersion NMR experiments and briefly describe their application to the study of allosteric dynamics in the homeodomain from the PBX transcription factor (PBX-HD). CPMG NMR data show that local folding (helix/coil) transitions in one part of PBX-HD help to communicate information between two distant binding sites. Furthermore, the combination of CPMG and other spin relaxation data show that this region can also undergo local misfolding, reminiscent of conformational ensemble models of allostery.