Crystallographic and nuclear magnetic resonance evaluation of the impact of peptide binding to the second PDZ domain of protein tyrosine phosphatase 1E.
Crystallographic and nuclear magnetic resonance evaluation of the impact of peptide binding to the second PDZ domain of protein tyrosine phosphatase 1E.
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DOI：
10.1021/bi101131f
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发表时间：
2010-11-02
期刊：
影响因子：
2.9
通讯作者：
Lee, Andrew L.
中科院分区：
文献类型：
--
作者：
Zhang, Jun;Sapienza, Paul J.;Ke, Hengming;Chang, Aram;Hengel, Sarah R.;Wang, Huanchen;Phillips, George N., Jr.;Lee, Andrew L.
PDZ（PSD 95/Discs large/ZO-1）结构域是在参与信号转导的支架蛋白中发现的普遍存在的蛋白质相互作用基序。尽管事实上许多PDZ显示出有限的倾向，经历结构变化，PDZ家族已与远程通信和变构。在结构和生物物理性质方面研究最多的PDZ结构域之一是来自蛋白酪氨酸磷酸酶1 E（PTP 1 E，也称为PTPL 1）的第二个PDZ（“PDZ 2”）结构域。先前，我们通过NMR弛豫研究表明，RA-GEF 2 C-末端肽底物的结合导致人PDZ 2中侧链动态变化的长距离传播[Fuentes等人，J. Mol.（2004），335，1105-1115]。在这里，我们提出了第一个X射线晶体结构的PDZ 2在不存在和存在的RA-GEF 2配体，解决的分辨率分别为1.65和1.3 μ m。这些结构与先前确定的NMR结构有些偏离，并且表明PDZ 2中非常微小的结构变化伴随肽结合。NMR残余偶极耦合确认的晶体结构是PDZ 2的时间平均原子坐标的精确模型。用来自APC的C-末端肽进一步测试对侧链动力学的影响，其显示出与RA-GEF 2几乎相同的结果。因此，由肽结合诱导的PDZ 2中的变构传递纯粹且稳健地通过动力学传递。15 N弛豫色散测量没有检测到动力学结构中间体的明显种群。总的来说，对于配体与PDZ 2的结合，这些数据从结构角度支持锁和钥匙结合模型，从动力学角度支持变构模型，它们共同表明了系综内功能转变的复杂能量景观。
PDZ (PSD95/Discs large/ZO-1) domains are ubiquitous protein interaction motifs found in scaffolding proteins involved in signal transduction. Despite the fact that many PDZs show a limited tendency to undergo structural change, the PDZ family has been associated with long-range communication and allostery. One of the PDZ domains studied most in terms of structure and biophysical properties is the second PDZ (“PDZ2”) domain from protein tyrosine phophatase 1E (PTP1E, also known as PTPL1). Previously we showed through NMR relaxation studies that binding of the RA-GEF2 C-terminal peptide substrate results in long-range propagation of side-chain dynamic changes in human PDZ2 [Fuentes, et al., J. Mol. Biol. (2004), 335, 1105-1115]. Here, we present the first X-ray crystal structures of PDZ2 in the absence and presence of RA-GEF2 ligand, solved to resolutions of 1.65 and 1.3 Å, respectively. These structures deviate somewhat from previously determined NMR structures, and indicate that very minor structural changes in PDZ2 accompany peptide binding. NMR residual dipolar couplings confirm the crystal structures to be accurate models of the time-averaged atomic coordinates of PDZ2. The impact on side-chain dynamics was further tested with a C-terminal peptide from APC, which showed near-identical results to that of RA-GEF2. Thus, allosteric transmission in PDZ2 induced by peptide binding is conveyed purely and robustly by dynamics. 15N relaxation dispersion measurements did not detect appreciable populations of a kinetic structural intermediate. Collectively, for ligand binding to PDZ2, these data support a lock-and-key binding model from a structural perspective and an allosteric model from a dynamical perspective, which together suggest a complex energy landscape for functional transitions within the ensemble.
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影响因子：
4.3
作者：
Ho BK;Agard DA
通讯作者：
Agard DA
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
8
作者：
Ho, Bosco K.;Agard, David A.
通讯作者：
Agard, David A.
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH
影响因子：
4.8
作者：
Gao, XL;Satoh, T;Kataoka, T
通讯作者：
Kataoka, T