The Morphology of Hydroxyapatite Nanoparticles Regulates Cargo Recognition in Clathrin-Mediated Endocytosis.
The Morphology of Hydroxyapatite Nanoparticles Regulates Cargo Recognition in Clathrin-Mediated Endocytosis.
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羟基磷灰石纳米颗粒的形态调节网格蛋白介导的内吞作用中的货物识别
DOI：
10.3389/fmolb.2021.627015
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发表时间：
2021
影响因子：
5
通讯作者：
Dong H
中科院分区：
文献类型：
--
作者：
Zhu C;Zhou X;Liu Z;Chen H;Wu H;Yang X;Zhu X;Ma J;Dong H
网格蛋白相关蛋白适应蛋白-2 （AP2）是异四聚体网格蛋白适应复合物家族的独特成员。它在许多细胞内囊泡运输途径中起着至关重要的作用。羟基磷灰石（HAp）纳米颗粒可以通过网格蛋白依赖的内吞作用进入细胞，诱导细胞凋亡，最终抑制肿瘤转移。探索AP2与HAp结合的微观过程，对了解HAp抗癌能力的分子机制具有重要意义。在这项工作中，我们利用分子模型研究了球形、棒状和针状纳米粒子在原子水平上与AP2蛋白的结合，发现不同纳米粒子的形态可以通过静电相互作用决定它们的结合特异性。我们的研究结果表明，球形HAp显著改变了AP2蛋白的构象，而针状HAp与AP2的结合能更大。因此，本研究为网格蛋白介导的内吞作用中的货物识别提供了一个微观图景，阐明了高效纳米生物材料的设计原则和可能的机制，并为其潜在的抗肿瘤治疗作用提供了基础。
The clathrin-associated protein adaptin-2 (AP2) is a distinctive member of the hetero-tetrameric clathrin adaptor complex family. It plays a crucial role in many intracellular vesicle transport pathways. The hydroxyapatite (HAp) nanoparticles can enter cells through clathrin-dependent endocytosis, induce apoptosis, and ultimately inhibit tumor metastasis. Exploring the micro process of the binding of AP2 and HAp is of great significance for understanding the molecular mechanism of HAp’s anti-cancer ability. In this work, we used molecular modeling to study the binding of spherical, rod-shaped, and needle-shaped HAps toward AP2 protein at the atomic level and found that different nanoparticles’ morphology can determine their binding specificity through electrostatic interactions. Our results show that globular HAp significantly changes AP2 protein conformation, while needle-shaped HAP has more substantial binding energy with AP2. Therefore, this work offers a microscopic picture for cargo recognition in clathrin-mediated endocytosis, clarifies the design principles and possible mechanisms of high-efficiency nano-biomaterials, and provides a basis for their potential anti-tumor therapeutic effects.
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影响因子：
5.8
作者：
Pronk, Sander;Pall, Szilard;Lindahl, Erik
通讯作者：
Lindahl, Erik
影响因子：
5.5
作者：
Best, Robert B.;Zhu, Xiao;Shim, Jihyun;Lopes, Pedro E. M.;Mittal, Jeetain;Feig, Michael;MacKerell, Alexander D., Jr.
通讯作者：
MacKerell, Alexander D., Jr.
影响因子：
4.4
作者：
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通讯作者：
KLEIN, ML
影响因子：
0.1
作者：
Chen, Ying;Wang, Jing;Zhang, Xingdong
通讯作者：
Zhang, Xingdong
影响因子：
3.7
作者：
Liu, Qingyu;Xue, Zhiyu;Xu, Dingguo
通讯作者：
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