Non-catalytic participation of the Pin1 peptidyl-prolyl isomerase domain in target binding
Non-catalytic participation of the Pin1 peptidyl-prolyl isomerase domain in target binding
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Pin1 肽基脯氨酰异构酶结构域在靶标结合中的非催化参与
DOI：
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
D. Litchfield
中科院分区：
文献类型：
--
作者：
Brendan T. Innes;M. Bailey;C. Brandl;B. Shilton;D. Litchfield
Pin1是一种磷酸化依赖性肽酰脯氨酸异构酶（PPIase），具有在蛋白激酶介导的信号通路中增加额外调节水平的潜力。此外，越来越多的证据表明，Pin1通过肽基-脯氨酸键上多种底物的异构化参与了神经变性和癌症病理表型的出现，其中脯氨酸之前的残基是磷酸化的丝氨酸或苏氨酸残基（即pS/T-P基序）。这个调控过程的关键步骤是Pin-1与其底物的相互作用。这是一个复杂的过程，因为Pin1由两个结构域组成，催化PPIase结构域和IV型WW结构域，这两个结构域都识别pS/T-P基序。观察到WW结构域对pS/T-P基序具有相当高的结合亲和力，这导致预测这两个结构域可能在介导Pin1对其底物的作用中具有不同的作用。为了评估其单个结构域在目标结合中的参与，我们进行了GST下拉来监测各种形式的Pin1和有丝分裂磷酸化蛋白之间的相互作用，发现了两类Pin-1相互作用蛋白，它们对PPIase结构域内残基的需求不同。根据这些观察结果，我们考虑了Pin1-底物相互作用的模型以及不同类别的Pin1相互作用蛋白的潜在功能。我们还比较了Pin1在其个体相互作用伙伴中识别的序列，以研究其不同类型相互作用的潜在基础。
Pin1 is a phosphorylation-dependent peptidyl-prolyl isomerase (PPIase) that has the potential to add an additional level of regulation within protein kinase mediated signaling pathways. Furthermore, there is a mounting body of evidence implicating Pin1 in the emergence of pathological phenotypes in neurodegeneration and cancer through the isomerization of a wide variety of substrates at peptidyl-prolyl bonds where the residue preceding proline is a phosphorylated serine or threonine residue (i.e., pS/T-P motifs). A key step in this regulatory process is the interaction of Pin-1 with its substrates. This is a complex process since Pin1 is composed of two domains, the catalytic PPIase domain, and a type IV WW domain, both of which recognize pS/T-P motifs. The observation that the WW domain exhibits considerably higher binding affinity for pS/T-P motifs has led to predictions that the two domains may have distinct roles in mediating the actions of Pin1 on its substrates. To evaluate the participation of its individual domains in target binding, we performed GST pulldowns to monitor interactions between various forms of Pin1 and mitotic phospho-proteins that revealed two classes of Pin-1 interacting proteins, differing in their requirement for residues within the PPIase domain. From these observations, we consider models for Pin1-substrate interactions and the potential functions of the different classes of Pin1 interacting proteins. We also compare sequences that are recognized by Pin1 within its individual interaction partners to investigate the underlying basis for its different types of interactions.
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DOI：
10.1073/pnas.80.10.2926
发表时间：
1983-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
DAVIS, FM;TSAO, TY;RAO, PN
通讯作者：
RAO, PN
影响因子：
56.9
作者：
Lu, PJ;Zhou, XZ;Lu, KP
通讯作者：
Lu, KP
影响因子：
16
作者：
X. Zhou;O. Kops;A. Werner;P. Lu;Minhui Shen;G. Stoller;Gerhard Küllertz;M. Stark;G. Fischer-G.
通讯作者：
X. Zhou;O. Kops;A. Werner;P. Lu;Minhui Shen;G. Stoller;Gerhard Küllertz;M. Stark;G. Fischer-G.
影响因子：
10.5
作者：
Shen, MH;Stukenberg, PT;Lu, KP
通讯作者：
Lu, KP
影响因子：
7
作者：
Crooks, GE;Hon, G;Brenner, SE
通讯作者：
Brenner, SE