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结构洞察揭示 Arap3 的 PH1 结构域对特定磷酯酰肌醇的识别。

Structural Insights Uncover the Specific Phosphoinositide Recognition by the PH1 Domain of Arap3.

机构信息

High Magnetic Field Laboratory, Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China.

Science Island Branch of Graduate School, University of Science and Technology of China, Hefei 230026, China.

出版信息

Int J Mol Sci. 2023 Jan 6;24(2):1125. doi: 10.3390/ijms24021125.

DOI:10.3390/ijms24021125
PMID:36674645
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9865853/
Abstract

Arap3, a dual GTPase-activating protein (GAP) for the small GTPases Arf6 and RhoA, plays key roles in regulating a wide range of biological processes, including cancer cell invasion and metastasis. It is known that Arap3 is a PI3K effector that can bind directly to PI(3,4,5)P3, and the PI(3,4,5)P3-mediated plasma membrane recruitment is crucial for its function. However, the molecular mechanism of how the protein recognizes PI(3,4,5)P3 remains unclear. Here, using liposome pull-down and surface plasmon resonance (SPR) analysis, we found that the N-terminal first pleckstrin homology (PH) domain (Arap3-PH1) can interact with PI(3,4,5)P3 and, with lower affinity, with PI(4,5)P2. To understand how Arap3-PH1 and phosphoinositide (PIP) lipids interact, we solved the crystal structure of the Arap3-PH1 in the apo form and complex with diC4-PI(3,4,5)P3. We also characterized the interactions of Arap3-PH1 with diC4-PI(3,4,5)P3 and diC4-PI(4,5)P2 in solution by nuclear magnetic resonance (NMR) spectroscopy. Furthermore, we found overexpression of Arap3 could inhibit breast cancer cell invasion in vitro, and the PIPs-binding ability of the PH1 domain is essential for this function.

摘要

Arap3 是一种双 GTPase 激活蛋白 (GAP)，可作用于小 GTPase Arf6 和 RhoA，在调节广泛的生物学过程中发挥关键作用，包括癌细胞侵袭和转移。已知 Arap3 是一种 PI3K 效应物，可直接与 PI(3,4,5)P3 结合，而 PI(3,4,5)P3 介导的质膜募集对其功能至关重要。然而，该蛋白如何识别 PI(3,4,5)P3 的分子机制尚不清楚。在这里，我们使用脂质体下拉和表面等离子体共振 (SPR) 分析发现，N 端第一个 pleckstrin 同源 (PH) 结构域 (Arap3-PH1) 可以与 PI(3,4,5)P3 相互作用，并且与 PI(4,5)P2 的亲和力较低。为了了解 Arap3-PH1 和磷酸肌醇 (PIP) 脂质如何相互作用，我们解析了 Arap3-PH1 在无配体形式和与二酰基磷脂酰肌醇 3,4,5-三磷酸 (diC4-PI(3,4,5)P3) 复合物的晶体结构。我们还通过核磁共振 (NMR) 光谱表征了 Arap3-PH1 与 diC4-PI(3,4,5)P3 和 diC4-PI(4,5)P2 的相互作用。此外，我们发现 Arap3 的过表达可以抑制乳腺癌细胞的体外侵袭，并且 PH1 结构域与 PIPs 的结合能力对于该功能至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b2f/9865853/e969dd813ec8/ijms-24-01125-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b2f/9865853/1e033d1fc9bc/ijms-24-01125-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b2f/9865853/c2d503e9849d/ijms-24-01125-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b2f/9865853/22f7848ec14e/ijms-24-01125-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b2f/9865853/e969dd813ec8/ijms-24-01125-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b2f/9865853/1e033d1fc9bc/ijms-24-01125-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b2f/9865853/c2d503e9849d/ijms-24-01125-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b2f/9865853/22f7848ec14e/ijms-24-01125-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b2f/9865853/e969dd813ec8/ijms-24-01125-g004.jpg

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本文引用的文献

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2
Local synthesis of the phosphatidylinositol-3,4-bisphosphate lipid drives focal adhesion turnover.局部合成的磷脂酰肌醇-3,4-二磷酸脂质驱动黏着斑周转。
Dev Cell. 2022 Jul 25;57(14):1694-1711.e7. doi: 10.1016/j.devcel.2022.06.011. Epub 2022 Jul 8.
3
Redefining the specificity of phosphoinositide-binding by human PH domain-containing proteins.
重新定义人类 PH 结构域蛋白对磷酸肌醇结合的特异性。
Nat Commun. 2021 Jul 15;12(1):4339. doi: 10.1038/s41467-021-24639-y.
4
Structural basis for the association of PLEKHA7 with membrane-embedded phosphatidylinositol lipids.PLEKHA7 与膜嵌入的磷脂酰肌醇脂质结合的结构基础。
Structure. 2021 Sep 2;29(9):1029-1039.e3. doi: 10.1016/j.str.2021.03.018. Epub 2021 Apr 19.
5
Membrane surface recognition by the ASAP1 PH domain and consequences for interactions with the small GTPase Arf1.ASAP1 PH结构域对膜表面的识别及其与小GTP酶Arf1相互作用的影响。
Sci Adv. 2020 Sep 30;6(40). doi: 10.1126/sciadv.abd1882. Print 2020 Sep.
6
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Biochem J. 2020 Oct 16;477(19):3791-3801. doi: 10.1042/BCJ20200300.
7
Multiple lipid binding sites determine the affinity of PH domains for phosphoinositide-containing membranes.多个脂质结合位点决定 PH 结构域与含有磷酸肌醇的膜的亲和力。
Sci Adv. 2020 Feb 19;6(8):eaay5736. doi: 10.1126/sciadv.aay5736. eCollection 2020 Feb.
8
Class II PI3K Functions in Cell Biology and Disease.PI3K 信号通路在细胞生物学和疾病中的作用 **解析**：PI3K 是磷酸肌醇 3-激酶的缩写，是一种脂质激酶。Class II PI3K 是其家族中的一种亚型，Class II PI3K Functions in Cell Biology and Disease 翻译为中文是“PI3K 信号通路在细胞生物学和疾病中的作用”。
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9
Alzheimer's amyloid-beta intermediates generated using polymer-nanodiscs.使用聚合物纳米盘生成的阿尔茨海默病淀粉样-β中间产物。
Chem Commun (Camb). 2018 Nov 13;54(91):12883-12886. doi: 10.1039/c8cc07921h.
10
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Chemphyschem. 2018 Oct 19;19(20):2603-2613. doi: 10.1002/cphc.201800444. Epub 2018 Jul 31.