Direct Investigation of Slow Correlated Dynamics in Proteins via Dipolar Interactions.
Direct Investigation of Slow Correlated Dynamics in Proteins via Dipolar Interactions.
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DOI：
10.1021/jacs.6b01447
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发表时间：
2016-07-13
影响因子：
15
通讯作者：
Vögeli B
中科院分区：
文献类型：
--
作者：
Fenwick RB;Schwieters CD;Vögeli B
当它们在微观状态之间转变时，天然状态运动的同步影响催化动力学，介导变构相互作用并降低蛋白质的构象熵。然而，它已被证明很难描述原生微观状态，因为它们通常是最小的挫折，并可能在μs-ms的时间尺度上相互转换。因此，直接观察协调的平衡波动将是描述蛋白质天然状态的重要工具。在这里，我们提出了一种策略，将偶极相互作用之间的NMR交叉相关弛豫（CCR）速率与单个连续HN-N和Hα-Cα键的残余偶极偶联（RDC）联系起来，这些键分别作为肽平面和侧链的代理。使用Xplor-NIH系综结构计算约束的RDC和CCR数据，我们观察到集体运动的时间尺度上慢于纳秒的骨干GB 3。为了直接访问CCR的相关性，我们开发了无结构数据分析。由此产生的动态相关图是一致的合奏约束的模拟，并揭示了一个复杂的网络。一般来说，我们发现，债券的运动平均略有相关，并在当地的环境占主导地位的许多意见。尽管如此，一些模式是典型的整个二级结构元素。在β折叠中，几乎所有的键都是弱相关的，并且存在与侧链的溶剂暴露/屏蔽交替对应的相关强度的近似二进制交替。对于α-螺旋，HN-N键中也存在弱相关性，并且涉及Hα-Cα键的相关程度直接受侧链波动的影响，而环则表现出复杂和不均匀的行为。
The synchronization of native state motions as they transition between microstates influences catalysis kinetics, mediates allosteric interactions and reduces the conformational entropy of proteins. However, it has proven difficult to describe native microstates because they are usually minimally frustrated and may interconvert on the μs-ms time scale. Direct observation of concerted equilibrium fluctuations would therefore be an important tool for describing protein native states. Here we propose a strategy that relates NMR cross-correlated relaxation (CCR) rates between dipolar interactions to residual dipolar couplings (RDCs) of individual consecutive HN–N and Hα–Cα bonds, which act as a proxy for the peptide planes and the side chains respectively. Using Xplor-NIH ensemble structure calculations restrained with the RDC and CCR data we observe collective motions on time scales slower than nanoseconds in the backbone for GB3. To directly access the correlations from CCR we develop a structure-free data analysis. The resulting dynamic correlation map is consistent with the ensemble-restrained simulations and reveals a complex network. In general we find that the bond motions are on average slightly correlated, and that the local environment dominates many observations. Despite this, some patterns are typical over entire secondary structure elements. In the β-sheet, nearly all bonds are weakly correlated and there is an approximately binary alternation in correlation intensity corresponding to the solvent exposure/shielding alternation of the side chains. For α-helices there is also a weak correlation in the HN-N bonds and the degree of correlation involving Hα-Cα bonds is directly affected by side-chain fluctuations, while loops show complex and non-uniform behavior.
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DOI：
10.1126/science.1186121
发表时间：
2010-02-05
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Hilser VJ
通讯作者：
Hilser VJ
DOI：
10.1007/s00249-011-0754-8
发表时间：
2011-12
影响因子：
2
作者：
Bryn Fenwick, R.;Esteban-Martin, Santi;Salvatella, Xavier
通讯作者：
Salvatella, Xavier
影响因子：
2.7
作者：
DELAGLIO, F;GRZESIEK, S;BAX, A
通讯作者：
BAX, A
影响因子：
2.7
作者：
BRUSCHWEILER R;BLACKLEDGE M;ERNST R R
通讯作者：
ERNST R R
影响因子：
--
作者：
HUBBARD, PS
通讯作者：
HUBBARD, PS