PH-dependent binding of the epsin ENTH domain and the AP180 ANTH domain to PI(4,5)P2-containing bilayers
PH-dependent binding of the epsin ENTH domain and the AP180 ANTH domain to PI(4,5)P2-containing bilayers
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DOI：
10.1016/j.jmb.2007.08.016
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发表时间：
2007-10-19
影响因子：
5.6
通讯作者：
Kutateladze, Tatiana G.
中科院分区：
文献类型：
--
作者：
Hom, Robert A.;Vora, Mohsin;Kutateladze, Tatiana G.
Epsin和AP 180是胞吞机制的重要组成部分，其控制蛋白质受体和细胞表面的其他大分子的内化。Epsin和AP 180通过其结构和功能相关的N-末端ENTH和ANTH结构域募集到质膜，所述结构域特异性识别PtdIns（4，5）P-2。在这里，我们表明，ENTH和ANTH结构域的膜锚定调节的酸性环境。降低pH增强了ENTH和ANTH结构域的PtdIns（4，5）P2亲和力，增强了它们与脂质囊泡和单层的结合。pH依赖性是由于保守的组氨酸残基的ENTH和ANTH结构域，质子化是必要的强PtdIns（4，5）P2识别，如脂质体结合，表面等离子体共振，NMR，单层表面张力和诱变实验所揭示的。ENTH和ANTH结构域的pH敏感性使人联想到FYVE结构域的pH依赖性，这表明PI结合结构域的子集具有膜锚定的共同调节机制。(C)2007爱思唯尔有限公司保留所有权利。
Epsin and AP180 are essential components of the endocytotic machinery, which controls internalization of protein receptors and other macromolecules at the cell surface. Epsin and AP180 are recruited to the plasma membrane by their structurally and functionally related N-terminal ENTH and ANTH domains that specifically recognize PtdIns(4,5)P-2. Here, we show that membrane anchoring of the ENTH and ANTH domains is regulated by the acidic environment. Lowering the pH enhances PtdIns(4,5) P2 affinity of the ENTH and ANTH domains reinforcing their association with lipid vesicles and monolayers. The pH dependency is due to the conserved histidine residues of the ENTH and ANTH domains, protonation of which is necessary for the strong PtdIns(4,5)P2 recognition, as revealed by liposome binding, surface plasmon resonance, NMR, monolayer surface tension and mutagenesis experiments. The pH sensitivity of the ENTH and ANTH domains is reminiscent to the pH dependency of the FYVE domain suggesting a common regulatory mechanism of membrane anchoring by a subset of the PI-binding domains. (C) 2007 Elsevier Ltd. All rights reserved.