Reconstruction of Coupled Intra- and Interdomain Protein Motion from Nuclear and Electron Magnetic Resonance.
Reconstruction of Coupled Intra- and Interdomain Protein Motion from Nuclear and Electron Magnetic Resonance.
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从核磁共振和电子核磁共振重建蛋白质结构域内和结构域间的耦合运动。
DOI：
10.1021/jacs.1c06289
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发表时间：
2021-10-06
影响因子：
15
通讯作者：
Vögeli B
中科院分区：
文献类型：
--
作者：
Born A;Soetbeer J;Breitgoff F;Henen MA;Sgourakis N;Polyhach Y;Nichols PJ;Strotz D;Jeschke G;Vögeli B
由多个结构域组成的蛋白质允许结构异质性和结构域间动力学，这可能对功能至关重要。畴内结构和动力学可以影响畴间构象，反之亦然。然而，没有建立的结构确定方法是目前可用的，可以探测这些运动的耦合。蛋白质Pin 1包含单独的调节和催化结构域，其采样“扩展”和“紧凑”状态，并且配体结合改变这种平衡。配体结合和结构域间距离已被证明会影响Pin 1的活性，表明结构域间变构。为了表征Pin 1的构象平衡，我们描述了一种新的方法来模拟在原子分辨率下使用多态系综的域内和域间动力学之间的耦合。该方法使用时间平均的核磁共振（NMR）的限制和双电子-电子共振（DEER）的数据，解决距离分布。虽然域内计算主要由精确的核奥弗豪泽增强（eNOE），J耦合和残余偶极耦合（RDC）驱动，但相对域分布由顺磁弛豫增强（PRE），RDC，域间NOE和DEER驱动。我们的数据支持载脂蛋白Pin 1的紧凑和扩展状态的70：30的人口。多态系综同时描述了这些构象，具有位于域间界面的不同构象差异，稳定了紧凑或扩展状态。我们还描述了催化位点和域间界面之间的相关构象，可以解释域间接触驱动的变构。
Proteins composed of multiple domains allow for structural heterogeneity and interdomain dynamics that may be vital for function. Intradomain structures and dynamics can influence interdomain conformations and vice versa. However, no established structure determination method is currently available that can probe the coupling of these motions. The protein Pin1 contains separate regulatory and catalytic domains that sample “extended” and “compact” states, and ligand binding changes this equilibrium. Ligand binding and interdomain distance have been shown to impact the activity of Pin1, suggesting interdomain allostery. In order to characterize the conformational equilibrium of Pin1, we describe a novel method to model the coupling between intra- and interdomain dynamics at atomic resolution using multi-state ensembles. The method uses time-averaged nuclear magnetic resonance (NMR) restraints and double electron-electron resonance (DEER) data that resolves distance distributions. While the intradomain calculation is primarily driven by exact nuclear Overhauser enhancements (eNOEs), J couplings, and residual dipolar couplings (RDCs), the relative domain distribution is driven by paramagnetic relaxation enhancement (PREs), RDCs, interdomain NOEs and DEER. Our data supports a 70:30 population of the compact and extended states in apo Pin1. A multi-state ensemble describes these conformations simultaneously, with distinct conformational differences located in the interdomain interface stabilizing the compact or extended states. We also describe correlated conformations between the catalytic site and interdomain interface that may explain allostery driven by interdomain contact.
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影响因子：
0.9
作者：
Born, Alexandra;Nichols, Parker J.;Henen, Morkos A.;Chi, Celestine N.;Strotz, Dean;Bayer, Peter;Tate, Shin-Ichi;Peng, Jeffrey W.;Vogeli, Beat
通讯作者：
Vogeli, Beat
DOI：
10.1021/acs.jpclett.0c03623
发表时间：
2021-02-18
期刊：
The journal of physical chemistry letters
影响因子：
--
作者：
Hays JM;Boland E;Kasson PM
通讯作者：
Kasson PM
影响因子：
5.6
作者：
Bouchard JJ;Xia J;Case DA;Peng JW
通讯作者：
Peng JW
影响因子：
2.7
作者：
Chi, Celestine N.;Strotz, Dean;Voegeli, Beat
通讯作者：
Voegeli, Beat
影响因子：
15
作者：
Baber, JL;Szabo, A;Tjandra, N
通讯作者：
Tjandra, N