Analysis of 15N-1H NMR relaxation in proteins by a combined experimental and molecular dynamics simulation approach: picosecond-nanosecond dynamics of the Rho GTPase binding domain of plexin-B1 in the dimeric state indicates allosteric pathways.
Analysis of 15N-1H NMR relaxation in proteins by a combined experimental and molecular dynamics simulation approach: picosecond-nanosecond dynamics of the Rho GTPase binding domain of plexin-B1 in the dimeric state indicates allosteric pathways.
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通过实验和分子动力学模拟相结合的方法分析蛋白质中的 15N-1H NMR 弛豫：二聚体状态下 plexin-B1 的 Rho GTPase 结合域的皮秒-纳秒动力学表明变构途径。
DOI：
10.1021/jp310142f
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Buck,Matthias
中科院分区：
文献类型：
--
作者：
Zerbetto,Mirco;Anderson,Ross;Bouguet-Bonnet,Sabine;Rech,Mariano;Zhang,Liqun;Meirovitch,Eva;Polimeno,Antonino;Buck,Matthias
我们研究plexin-B1的Rho-GTbinding Domain（RBD）的皮秒-纳秒动力学，其在plexin介导的细胞信号传导中起关键作用。用无模型（MF）方法和慢松弛局域结构/分子动力学（SRLS-MD）方法对二聚体RBD的骨架15 N弛豫数据进行了分析。独立分析的MD轨迹，MF范式的基础上，也进行。MF是一种广泛流行的简单方法，SRLS是一种通用方法，SRLS-MD是我们最近开发的一种集成方法。比较了RBD二聚体、先前研究的RBD单体突变体以及先前研究的后者与GTPase Rac 1的复合物的相应参数。丛蛋白-B1 RBD的L2、L3和L4环分别参与与其他丛蛋白结构域的相互作用、GT3结合和RBD二聚化。发现在单体和二聚体RBD的环中的肽基团经历弱的和适度不对称的局部有序，大约以Ci-1α-Ciα轴为中心，和纳秒主链运动。二聚体的α-螺旋和β-链（单体的β-链）中的肽基团经历了大约以Ci-1α-Ciα轴（N-H键）为中心的强且高度不对称的局部有序化。N-H涨落发生在皮秒时间尺度上。一个变构途径GT3结合，提供新的见解丛蛋白功能，划定。
We investigate picosecond–nanosecond dynamics of the Rho-GTPase Binding Domain (RBD) of plexin-B1, which plays a key role in plexin-mediated cell signaling. Backbone15N relaxation data of the dimeric RBD are analyzed with the model-free (MF) method, and with the slowly relaxing local structure/molecular dynamics (SRLS-MD) approach. Independent analysis of the MD trajectories, based on the MF paradigm, is also carried out. MF is a widely popular and simple method, SRLS is a general approach, and SRLS-MD is an integrated approach we developed recently. Corresponding parameters from the RBD dimer, a previously studied RBD monomer mutant, and the previously studied complex of the latter with the GTPase Rac1, are compared. The L2, L3, and L4loops of the plexin-B1 RBD are involved in interactions with other plexin domains, GTPase binding, and RBD dimerization, respectively. Peptide groups in the loops of both the monomeric and dimeric RBD are found to experience weak and moderately asymmetric local ordering centered approximately at the Ci–1α–Ciαaxes, and nanosecond backbone motion. Peptide groups in the α-helices and the β-strands of the dimer (the β-strands of the monomer) experience strong and highly asymmetric local ordering centered approximately at the Ci–1α–Ciαaxes (N–H bonds). N–H fluctuations occur on the picosecond time scale. An allosteric pathway for GTPase binding, providing new insights into plexin function, is delineated.
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DOI：
10.1016/j.str.2009.06.008
发表时间：
2009-08-12
期刊：
Structure (London, England : 1993)
影响因子：
--
作者：
del Sol A;Tsai CJ;Ma B;Nussinov R
通讯作者：
Nussinov R
影响因子：
2.9
作者：
Finerty, PJ;Mittermaier, AK;Forman-Kay, JD
通讯作者：
Forman-Kay, JD
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影响因子：
2.7
作者：
Addi Fadel;Danqing Jin;G. Montelione;R. Levy
通讯作者：
R. Levy
核磁共振自旋弛豫的蛋白质动力学：缓慢弛豫的局部结构视角
DOI：
--
发表时间：
2011
期刊：
影响因子：
--
作者：
E. Meirovitch;A. Polimeno;J. Freed
通讯作者：
J. Freed
影响因子：
3.3
作者：
Maragakis, Paul;Lindorff-Larsen, Kresten;Shaw, David E.
通讯作者：
Shaw, David E.